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Supported by Eli Lilly and Company.
Eli Lilly and Company has not influenced the content of this publication
Developed in association with theEuropean Thoracic Oncology Platform
28–31 January 2021
IASLC 2020 World Conference on Lung Cancer
Letter from Prof Rolf Stahel
Dear Colleagues
It is my pleasure to present this ETOP slide set which has been designed to highlight and summarise key findings in
thoracic cancers from the major congresses in 2020. This slide set specifically focuses on the IASLC 2020 World
Conference on Lung Cancer and is available in 4 languages – English, French, Chinese and Japanese.
The area of clinical research in oncology is a challenging and ever changing environment. Within this environment we all
value access to scientific data and research which helps to educate and inspire further advancements in our roles as
scientists, clinicians and educators. I hope you find this review of the latest developments in thoracic cancers of benefit to
you in your practice. If you would like to share your thoughts with us we would welcome your comments. Please send any
correspondence to [email protected].
I would like to thank our ETOP members Drs Solange Peters and Martin Reck for their roles as Editors – for prioritising
abstracts and reviewing slide content. The slide set you see before you would not be possible without their commitment and
hard work.
Finally, we are also very grateful to Lilly Oncology for their financial, administrative and logistical support in the realisation of
this complex yet rewarding activity.
Yours sincerely,
Rolf Stahel
President, ETOP Foundation Council
ETOP Medical Oncology Slide Deck Editors 2020
Focus: NSCLC (all stages)
Dr Solange Peters
Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland
Focus: Other malignancies, SCLC, mesothelioma, rare tumours
Dr Martin Reck
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany
4
Contents
• Screening, biomarkers and prevention
• Early stage and locally advanced NSCLC – Stages I, II and III
• Advanced NSCLC – Not radically treatable stage III and stage IV
– First line
– Later lines
• Other malignancies
– SCLC, mesothelioma and thymic epithelial tumors
Screening, biomarkers and prevention
6
PS01.02: National Lung Cancer Screening Program in Taiwan: The TALENT Study – Yang P-C, et al
• Study objective
– To assess the feasibility of a national lung cancer screening program for detecting lung cancer in never-
smokers with a high-risk in the Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT)
*2/7 days with cooking by pan-frying, stir-frying or deep-frying in
1 week (max. 21) x years with cooking Yang P-C, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.02
Bx/follow-up
Bx/follow-up
Key patient inclusion criteria
• Never smokers or former light smoker <10 pack-
years and had quit >15 years
• 55–75 years old
• One of following risks:
• Family history of lung cancer (≤3rd degree)
• Environmental tobacco smoking history
• Chronic lung disease (TB, COPD)
• Cooking index* ≥110
• Cooking without using ventilation
(n=12,011; 50% with a family history)
Low-dose chest CT
Biomarkers (blood, urine)
Questionnaire
Standard contrast-
enhanced chest CT
CXR
Positive
Negative
Positive
Positive
7
PS01.02: National Lung Cancer Screening Program in Taiwan: The TALENT Study – Yang P-C, et al
• Key results
*Ground glass opacity >5 mm, solid/part solid >6 mm Yang P-C, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.02
N=12,011
T0 lung cancer detection rate, % 2.6
Invasive lung cancer, % 2.1
Multiple primary lung cancer, % 17.9
LDCT positive*, % 17.4
Invasive procedures, % 3.4
Stage 0–I lung cancer confirmed, % 96.5
Prevalence of lung cancer, %
With family history
Without family history
3.2
2.0
Histologic diagnosis, n n=313
Adenocarcinoma in situ 58
Minimally invasive adenocarcinoma 71
Invasive adenocarcinoma 183
Adenosquamous carcinoma 1
Stage, n n=313
0 58
IA 218
IB 26
IIA 0
IIB 3
IIIA 2
IIIB 1
IV 5
Family history
(degree)
All lung
cancer, %
Invasive lung
cancer, %
0 2.0 1.6
1 3.1 2.5
2 4.0 3.7
3 6.7 5.3
≥4 9.1 9.1
p-value <0.001 <0.001
8
PS01.02: National Lung Cancer Screening Program in Taiwan: The TALENT Study – Yang P-C, et al
• Key results (cont.)
• Conclusions
– Using a national lung cancer screening program may be feasible to detect lung cancer in high-risk never-
smokers and those with a first-degree family history of lung cancer may be at increased risk
Yang P-C, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.02
Absence, n/N (%) Presence, n/N (%) RR (95%CI) p-value
Lung cancer family history 120/6002 (2.0) 193/6009 (3.2) 1.61 (1.28, 2.01) <0.001
First-degree relative 127/6432 (2.0) 186/5579 (3.3) 1.69 (1.35, 2.11) <0.001
Father 281/10,377 (2.7) 32/1634 (2.0) 0.72 (0.50, 1.04) 0.077
Mother 251/10,241 (2.5) 62/1770 (3.5) 1.43 (1.09, 1.88) 0.010
Brother 260/10,901 (2.4) 53/1110 (4.8) 2.00 (1.50, 2.67) <0.001
Sister 244/10,367 (2.4) 69/1644 (4.2) 1.78 (1.37, 2.32) <0.001
Second-degree relative 307/11,645 (2.6) 6/366 (1.6) 0.62 (0.28, 1.39) 0.238
Third-degree relative 312/11,947 (2.6) 1/64 (1.6) 0.60 (0.09, 4.20) 1.000
Environmental tobacco exposure 53/1999 (2.7) 254/9923 (2.6) 0.97 (0.72, 1.29) 0.813
Chronic lung disease history 284/10,568 (2.7) 19/1142 (1.7) 0.62 (0.39, 0.98) 0.038
Cooking index ≥110 209/7591 (2.8) 104/4395 (2.4) 0.86 (0.68, 1.08) 0.201
Cooking without ventilation 306/11,800 (2.6) 7/211 (3.3) 1.28 (0.61, 2.67) 0.513
9
OA07.06: Interdependence of KRAS and TP53 Mutations in Predicting ICI Efficacy in EGFR/ALK WT Non-Squamous NSCLC: Results From 1129 Patient-Level Data – Li L, et al
• Study objective
– To assess the interdependence of KRAS and TP53 mutations for predicting the efficacy of immune
checkpoint inhibitors in patients with EGFR or ALK WT nonsquamous NSCLC
• Methods
– Clinical and mutational data was collected from 1129 patients with EGFR or ALK WT nonsquamous NSCLC
who received immune checkpoint inhibitors from 8 cohorts (3DMed, SNCC, Van Allen, Rizvi-34, Rizvi-240,
MSKCC-75, MSKCC-350 and POPLAR/OAK)
– The impact of KRAS and TP53 mutations on ORR, PFS and OS was assessed
Li L, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.06
10
OA07.06: Interdependence of KRAS and TP53 Mutations in Predicting ICI Efficacy in EGFR/ALK WT Non-Squamous NSCLC: Results From 1129 Patient-Level Data – Li L, et al
• Key results
– A longer PFS by immunotherapy, but not prolongation of PFS by chemotherapy, was found in patients with
TP53 and KRAS co-mutations although there was no association with TP53 or KRAS mutation alone
Li L, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.06
ORR, % mPFS, mo
TK (76) 50.0 10.48
T-only (209) 23.4 3.10
K-only (101) 16.7 2.77
WT (238) 14.3 3.23
Meta-cohort PFS
35302520151050
PF
S,
%
100
75
50
25
0
Log-rank p<0.001
Time, months
POPLAR/OAK PFS (docetaxel)
35302520151050
PF
S,
%
100
75
50
25
0
Log-rank p=0.032
Time, months
ORR, % mPFS, mo
TK (13) 7.7 2.86
T-only (82) 11.0 2.89
K-only (15) 13.3 2.86
WT (134) 18.7 4.30
11
OA07.06: Interdependence of KRAS and TP53 Mutations in Predicting ICI Efficacy in EGFR/ALK WT Non-Squamous NSCLC: Results From 1129 Patient-Level Data – Li L, et al
• Key results (cont.)
• Conclusions
– In patients with nonsquamous NSCLC, the combination of KRAS and TP53 mutations are interdependent
for predicting the benefit of immune checkpoint inhibitors; better ORR and PFS was observed in those
who were EGFR/ALK WT
Li L, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.06
Totality Variable
ORR PFS OS
RR (95%CI) p-value RR (95%CI) p-value RR (95%CI) p-value
All TP53-mut vs. TP53-WT 1.94 (1.31, 2.87) 0.001 0.72 (0.55, 0.95) 0.019 1.21 (0.98, 1.50) 0.071
All KRAS-mut vs. KRAS-WT 1.54 (1.02, 2.32) 0.040 0.82 (0.56, 1.19) 0.295 1.01 (0.70, 1.47) 0.947
KRAS-mut TP53-mut vs. TP53-WT 2.86 (1.46, 5.57) 0.002 0.47 (0.32, 0.68) <0.001 0.75 (0.51, 1.12) 0.159
KRAS-WT TP53-mut vs. TP53-WT 1.53 (0.92, 2.56) 0.104 0.91 (0.65, 1.27) 0.566 1.47 (1.14, 1.91) 0.003
TP53-mut KRAS-mut vs. KRAS-WT 1.98 (1.17, 3.35) 0.011 0.66 (0.47, 0.93) 0.017 0.73 (0.51, 1.04) 0.078
TP53-WT KRAS-mut vs. KRAS-WT 1.28 (0.61, 2.71) 0.518 1.04 (0.60, 1.79) 0.885 1.19 (0.79, 1.77) 0.338
All TP53/KRAS-co-mut vs. rest 2.59 (1.63, 4.12) <0.001 0.58 (0.43, 0.79) 0.001 0.86 (0.62, 1.18) 0.356
12
OA07.08: HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed, Phase II Platform Study in Patients with NSCLC, who Progressed on Anti-PD(L)1 Therapy – Besse B, et al
• Study objective
– To assess the efficacy and safety of durvalumab-based combinations in patients with metastatic NSCLC who
progressed on an anti-PD-(L)1-containing therapy
Besse B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.08
Primary endpoint
• ORR
Secondary endpoints
• PFS, OS, DCR, safety
Durvalumab + ceralasertib (ATR)
Durvalumab + olaparib (PARP)Key patient inclusion criteria
• Locally advanced or
metastatic NSCLC
• Tumour progression on anti-
PD-(L)1
• Prior platinum-doublet
chemotherapy
• No EGFR, ALK, ROS1,
BRAF, MET or RET
alterations
(n=617)
Durvalumab + oleclumab (anti-CD73)
Durvalumab + trastuzumab deruxtecan (HER2)
Durvalumab + cediranib (VEGF)
Part A:
Biomarker
matched
(n=85)
Part B:
Biomarker
non-matched
(n=177)
Durvalumab + danvatirsen (STAT3)
Durvalumab + ceralasertib (ATR)
Durvalumab + olaparib (PARP)
Durvalumab + oleclumab (anti-CD73)
Durvalumab + danvatirsen (STAT3)
Durvalumab + ceralasertib (ATR)
Durvalumab + olaparib (PARP)
Durvalumab + oleclumab (anti-CD73)
Durvalumab + olaparib (PARP)
Durvalumab + trastuzumab deruxtecan (HER2)
ATM
STK11
CD73
HER2e
HRRm
HER2m
Primary
resistance
(n=74)
Acquired
resistance
(n=103)
13
Olaparib = PARP inhibitor, danvatirsen = STAT 3 inhibitor, ceralasertib = ATR inhibitor,
oleclumab = anti-CD73
OA07.08: HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed, Phase II Platform Study in Patients with NSCLC, who Progressed on Anti-PD(L)1 Therapy – Besse B, et al
• Key results
Besse B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.08
Progression-free survival Overall survival
015911153687
01381745
011312223962
0161657
Olaparib + durvalumab
Danvatirsen + durvalumab
Ceralasertib + durvalumab
Oleclumab + durvalumab
Time, months
Pro
ba
bili
ty o
f P
FS
1.0
0.8
0.6
0.4
0.2
0
211815129630
Time, months
Pro
babili
ty o
f O
S
1.0
0.8
0.6
0.4
0.2
0
302724211815129630
07918273442517387
02471219263445
02172336425562
03614294257
Olaparib + durvalumab
Danvatirsen + durvalumab
Ceralasertib + durvalumab
Oleclumab + durvalumab
No. at risk
14
OA07.08: HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed, Phase II Platform Study in Patients with NSCLC, who Progressed on Anti-PD(L)1 Therapy – Besse B, et al
• Key results (cont.)
• Conclusions
– In patients with NSCLC who have failed on anti-PD-(L1), use of molecular stratification is feasible
– Durvalumab + ceralasertib demonstrated preliminary promising activity
Besse B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.08
Durvalumab combination n ORR, n (%) mPFS, mo (80%CI) mOS, mo (80%CI)B
iom
ark
er
se
lec
ted
Olaparib HRR 21 2 (9.5) 2.79 (1.48, 5.26) 9.63 (5.26, 15.97)
Olaparib STK11 21 1 (4.8) 1.41 (1.38, 1.81) 5.75 (5.29, 10.84)
Ceralasertib ATM 18 2 (11.1) 7.43 (3.45, 9.46) 15.80 (11.01, NC)
Oleclumab 73H 23 0 (0) 1.58 (1.41, 2.76) 9.49 (7.49, NC)
Pri
ma
ry
res
ista
nce Olaparib 22 0 (0) 3.38 (2.10, 4.93) 7.16 (4.93, 10.28)
Danvatirsen 23 0 (0) 1.68 (1.64, 2.99) 6.01 (3.55, 6.51)
Ceralasertib 20 2 (10.5) 4.24 (1.94, 6.77) 11.60 (10.45, NC)
Oleclumab 9 0 (0) 1.41 (1.35, 1.81) 7.06 (4.90, 7.06)
Ac
qu
ire
d
res
ista
nce Olaparib 23 1 (4.3) 4.17 (2.69, 4.37) 15.51 (8.80, 19.75)
Danvatirsen 22 0 (0) 3.09 (2.83, 6.14) 11.20 (9.72, 12.55)
Ceralasertib 24 2 (8.3) 4.96 (3.55, 5.98) 17.38 (14.06, NC)
Oleclumab 25 1 (4.2) 2.63 (1.64, 2.79) 12.78 (6.14, 12.78)
15
MA08.10: LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis – Mack PC, et al
• Study objective
– To assess the feasibility of using plasma ctDNA as a screening approach in patients with advanced NSCLC
• Methods
– Plasma samples and fresh tissue biopsies were collected from patients (n=129) undergoing LUNGMAP
screening for ctDNA testing using FoundationONE CDx and FoundationACT platforms
– Sensitivity was determined as the proportion of patients with drivers in both ctDNA and tissue and specificity
was determined as the proportion of patients without drivers in ctDNA and tissue using tissue-detected driver
alterations as the gold standard
Mack PC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA08.10
16*Mostly point mutations
MA08.10: LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis – Mack PC, et al
• Key results
– For cases with matched tissue and plasma, 54 of 129 patients had driver oncogenes (EGFR, KRAS, RET,
MET, BRAF) detected with a sensitivity of 83% and specificity of 97%
Mack PC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA08.10
3.7
32.0
79.6
54.0
16.7 14.0
0%
20%
40%
60%
80%
100%
Driver only (n=54) Short variants*
Tissue only
Both
ctDNA only
Detection in ctDNA and tissue
17
MA08.10: LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis – Mack PC, et al
• Conclusions
– The findings suggest that ctDNA can be used for enrolling patients in LUNGMAP sub-studies, particularly for
those with positive results although negative results should be considered inconclusive
Mack PC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA08.10
Early stage and locally advanced NSCLC –Stages I, II and III
19
PS01.04: International Tailored Chemotherapy Adjuvant Trial: ITACA Trial. Final Results – Novello S, et al
• Study objective
– To compare adjuvant pharmacogenomics-driven (tailored) chemotherapy, based on thymidylate synthase
(TS) and excision-repair cross-complementing-1 (ERCC1) gene expression versus standard adjuvant
chemotherapy
*Cisplatin-doublet, investigator choice Novello S, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.04
Primary endpoint
• OS (5-year rate)
Secondary endpoints
• RFS, safety
Stratification
• Stage II vs. III and smoking status
Profile 2: ERCC1 high, TS low
Profile 3: ERCC1 low, TS high
Profile 1: ERCC1 high, TS high
Key patient inclusion criteria
• Completely resected (R0)
NSCLC
• Stage II–IIIA
• ECOG PS 0–1
(n=733)
Profile 4: ERCC1 low, TS, low
Paclitaxel alone (n=148)
Control arm* (n=144)
Control arm* (n=47)
Control arm* (n=106)
Control arm* (n=92)
Pemetrexed alone (n=43)
Cisplatin-gemcitabine (n=101)
Cisplatin-pemetrexed (n=92)
Cisplatin not
allowed in the
tailored arm
Cisplatin
allowed in the
tailored arm
20
PS01.04: International Tailored Chemotherapy Adjuvant Trial: ITACA Trial. Final Results – Novello S, et al
• Key results
Novello S, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.04
Overall survival Recurrence-free survival
Tailored arm (n=344) Control arm (n=346)
mRFS, months (95%CI) 64.4 (34.7, 96.4) 41.5 (29.2, 58.1)
HR (95%CI) 0.94 (0.74, 1.20)
Tailored arm (n=344) Control arm (n=346)
mOS, months (95%CI) 96.4 (81.8, NR) 83.5 (60.1, NR)
HR (95%CI) 0.76 (0.55, 1.04)
820354978108156239344
817334874110155221346Control
Pro
po
rtio
n o
f p
atie
nts
aliv
e
1.00
0.75
0.50
0.25
0
Time since randomisation, months96847260483624120
No. at risk
Tailored
Tailored
Control
O
68
86
E
78.5
75.5
Log-rank test
Chi2=2.864, p=0.091
81831447092126208344
81429406793128201346ControlP
rop
ort
ion o
f re
cu
rre
nce-f
ree
pa
tie
nts
1.00
0.75
0.50
0.25
0
Time since randomisation, months96847260483624120
No. at risk
Tailored
Tailored
Control
O
128
132
E
132.1
127.9
Log-rank test
Chi2=0.253, p=0.615
21
PS01.04: International Tailored Chemotherapy Adjuvant Trial: ITACA Trial. Final Results – Novello S, et al
• Key results (cont.)
Novello S, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.04
Overall survival Recurrence-free survivalOS / RFS
predictor
Age
<70 years
≥70 years
Sex
Male
Female
Smoking habit
Never/former smoker
Active smoker
ECOG PS
0
1
Stage
II
IIIA
Histology
Adeno CA
Squamous cell CA
Other
Primary surgery
Lobectomy
Pneumonectomy
Other
HR
(95%CI)
No. of OS events/
patients
Hazard
ratio
p-
value
0.5 1.0 1.5 2.0
110/533
44/157
114/474
40/214
79/341
75/349
111/515
36/156
88/406
66/282
91/407
51/239
12/43
106/475
30/97
11/58
0.80 (0.55, 1.17)
0.70 (0.39, 1.27)
0.79 (0.55, 1.14)
0.67 (0.36, 1.24)
0.64 (0.41, 1.00)
0.93 (0.59, 1.46)
0.72 (0.50, 1.05)
0.96 (0.50, 1.85)
0.62 (0.41, 0.94)
1.03 (0.63, 1.67)
0.75 (0.50, 1.14)
0.76 (0.44, 1.32)
0.79 (0.25, 2.47)
0.76 (0.52, 1.11)
0.76 (0.37, 1.59)
1.06 (0.32, 3.48)
0.70
0.65
0.26
0.46
0.12
1.00
0.87
No. of RFS events/
patients
HR
(95%CI)
p-
value
0.5 1.0 1.5 2.0
196/533
64/157
182/474
78/214
124/341
136/349
196/515
57/156
138/406
121/282
162/407
78/239
20/43
183/475
47/97
19/58
0.98 (0.74, 1.30)
0.87 (0.53, 1.43)
1.01 (0.75, 1.35)
0.80 (0.52, 1.26)
0.85 (0.59, 1.20)
1.02 (0.73, 1.43)
0.98 (0.74, 1.29)
0.85 (0.50, 1.43)
0.84 (0.60, 1.17)
1.09 (0.76, 1.56)
0.94 (0.69, 1.28)
1.04 (0.66, 1.63)
0.57 (0.24, 1.39)
0.90 (0.67, 1.20)
0.89 (0.49, 1.60)
1.13 (0.46, 2.79)
0.68
0.41
0.46
0.64
0.29
0.50
0.89
Tailored better Control better
Hazard
ratio
Tailored better Control better
22
PS01.04: International Tailored Chemotherapy Adjuvant Trial: ITACA Trial. Final Results – Novello S, et al
• Key results (cont.)
• Conclusions
– In patients with completely resected NSCLC, using a tailored approach to select adjuvant chemotherapy did
not significantly improve survival although it was associated with an improved safety profile and a trend
towards improved efficacy
Novello S, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.04
Grade 3–4 AEs occurring in ≥1%, n (%) Tailored arm Control arm
Neutropenia 45 (13.4) 64 (18.9)
Leukopenia 13 (3.9) 45 (13.3)
Nausea 13 (3.9) 15 (4.4)
Thrombocytopenia 11 (3.3) 26 (7.7)
Fatigue 9 (2.7) 5 (1.5)
Vomiting 7 (2.1) 6 (1.8)
Alopecia 7 (2.1) 0 (0)
Diarrhoea 5 (1.5) 1 (0.3)
Anaemia 3 (0.9) 9 (2.7)
Asthenia 1 (0.3) 5 (1.5)
23
PS01.05: Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis – Lee JM, et al
• Study objective
– To assess the surgical and clinical outcomes of neoadjuvant atezolizumab in patients with resectable stage
1B–IIIB NSCLC
Lee JM, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.05
Atezolizumab
1200 mg q3w
(2 cycles)
Key patient inclusion criteria
• Stage IB–IIIB resectable
NSCLC
• Treatment naïve
• ECOG PS 0–1
(n=181)
Primary endpoint
• MPR (≤10% viable tumour cells)
Secondary endpoints
• MPR by PD-L1 status, TMB, safety
Surgical
resection
Adjuvant
atezolizumab
1200 mg q3w
(12 months)
Clinical
benefit
24
PS01.05: Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis – Lee JM, et al
• Key results
– Following atezolizumab, 66 (43%) patients were down-staged and 29 (19%) patients were up-staged
Lee JM, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.05
Downstaging, %
Pre-treatment cStage
(n=155)
Post-treatment cStage
(n=155)
ypT0N0M0 0 5
IA 0 11
IB 10 8
IIA 12 6
IIB 30 23
IIIA 39 27
IIIB 9 4
IV 0 1
n (%) n=159
Surgical approach Thoracotomy 73 (46)
Robotic 59 (37)
VATS 27 (17)
Extent of resection Lobectomy 125 (79)
Pneumonectomy 14 (9)
Bilobectomy 10 (6)
No resection 5 (3)
Wedge 3 (2)
Segmentectomy 2 (1)
Completeness of resection R0 145 (92)
R1 7 (4)
R2 7 (4)
25
PS01.05: Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis – Lee JM, et al
• Key results (cont.)
• Conclusions
– In patients with resectable stage IB–IIIB NSCLC, neoadjuvant atezolizumab was generally well-tolerated and
resection was performed with low perioperative morbidity and mortality as well as with a high R0 rate
Lee JM, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.05
n=159
Intra-operative event, n (%)
Bronchial complications 1 (1)
Vascular complications 4 (3)
Median length of hospitalisation, days (range) 7.5 (2–68)
Deaths, n (%)
Before surgery 0
≤30 days after surgery1 (0.6)
[sudden death]
30–90 days after surgery1 (0.6)
[pneumonitis]
AEs, n (%)
TRAE irAEs
Pre-op
(n=181)
Post-op
(n=159)
Pre-op
(n=181)
Post-op
(n=159)
Grade 1 55 (30) 13 (8) 22 (12) 18 (11)
Grade 2 36 (20) 18 (11) 16 (9) 12 (8)
Grade 3 11 (6) 17 (11) 3 (2) 11 (7)
Grade 4 0 (0) 3 (2) 0 (0) 1 (1)
Grade 5 0 (0) 1 (1) 0 (0) 1 (1)
26
OA06.06: Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study – Carbone DP, et al
• Study objective
– To assess the clinical and biomarker data of neoadjuvant atezolizumab in treatment naïve patients with
resectable stage 1B–IIIB NSCLC
Carbone DP, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.06
Atezolizumab
1200 mg q3w
(2 cycles)
Key patient inclusion criteria
• Stage IB–IIIB resectable
NSCLC
• Treatment naïve
• ECOG PS 0–1
(n=181)
Primary endpoint
• MPR (≤10% viable tumour cells)
Secondary endpoints
• MPR by PD-L1 status, TMB, safety
Surgical
resection
Adjuvant
atezolizumab
1200 mg q3w
(12 months)
Clinical
benefit
27
OA06.06: Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study – Carbone DP, et al
• Key results
*Analysis population excluded EGFR and ALK positive patients; †calculated in the primary
efficacy population with TMB results; ‡local TPS score used if central score was not available Carbone DP, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.06
PD-L1 IHC at screening‡
p=0.30 p=0.089
TPS
<1%
TPS
≥1%
TPS
<50%
TPS
≥50%
Pathologic response
in the primary efficacy
population (n=144)
MPR rate*
(primary efficacy population
with known PD-L1 status, n=118)
<10 ≥10 <16 ≥16
TMB cut-off (mut/Mb)
MPR rate† by TMB cut-off
for all histologies (n=71)
MP
R,
%
50
40
30
20
10
0
MPR
pCR
21%
7%
10/144
13%
25%
7/53 16/65 8/73 15/45 8/51 6/20 9/59 5/12
30/14411%
33%
16%
30%
15%
42%p=0.162 p=0.004
28
OA06.06: Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study – Carbone DP, et al
• Key results (cont.)
• Conclusions
– In patients with resectable stage IB–IIIB NSCLC, neoadjuvant atezolizumab met the primary endpoint of
improvement in MPR rate and better pathologic responses were observed in those with high PD-L1
expression (TPS ≥50%) and higher TMB (≥16 mut/Mb)
Carbone DP, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.06
Events, n (%) 12-mo rate, % 18-mo rate, %
OS
Disease stage Stage I/II
Stage III
13 (18)
8 (11)
92
95
91
87
MPR No
Yes
17 (16)
2 (7)
92
96
87
92
DFS
MPR No
Yes
26 (24)
3 (10)
82
93
74
89
29
OA06.03: Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC – Majem M, et al
• Study objective
– To assess the patient-reported outcomes of adjuvant osimertinib in patients with early stage EGFR-mutant
NSCLC
*Data previously reported Majem M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.03
Primary endpoint
• DFS in stage II/IIIA patients
(investigator assessment)*
Secondary endpoints
• DFS in overall population*, OS, safety,
HRQoL (SF-36)
R
1:1
PD/3 years/
discontinuation
PD/3 years/
discontinuation
Stratification
• Stage (IB vs. II vs. IIIA)
• EGFRm (Ex19del vs. L858R)
• Race (Asian vs. non-Asian)
Key patient inclusion criteria
• Completely resected stage IB,
II, IIIA NSCLC
• Confirmed EGFR mutation
(Ex19del/L858R)
• With or without adjuvant
chemotherapy
• WHO PS 0–1
(n=682)
Placebo QD
(n=343)
Osimertinib 80 mg QD
(n=339)
30
OA06.03: Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC – Majem M, et al
• Key results
Majem M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.03
PCS MCS
SF-36 component
Mixed model of repeated measures –
adjusted mean change from baseline (95%CI)
Definition of clinically meaningful change based
on the 3rd edition of the SF-36 scoring manual
Osimertinib Placebo Osimertinib - placebo
PCS 1.13 (0.54, 1.72) 2.31 (1.70, 2.91) -1.18 (-2.02, -0.34) ±2
MCS 1.34 (0.60, 2.08) 2.68 (1.92, 3.44) -1.34 (-2.40, -0.28) ±3
Me
an
(S
D)
ch
an
ge
fro
m b
ase
line
Osimertinib
Placebo20
10
0
-10
-20
9672482412Time, weeks
165212261274291
124172219275301
Osimertinib
Placebo
No. at risk
20
10
0
-10
-20
9672482412Time, weeks
165212261274291
124172219275301
Osimertinib
Placebo
No. at risk
31
OA06.03: Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC – Majem M, et al
• Key results (cont.)
• Conclusions
– In patients with resected EGFR-mutant NSCLC, there were no differences between adjuvant osimertinib and
placebo for changes from baseline to Week 96 or time to deterioration in HRQoL measures
*HR <1 favours osimertinib Majem M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.03
Time to deterioration of
SF-36 health domains
Osimertinib
(n=339), n (%)
Placebo
(n=343), n (%) HR
Bodily pain 53 (15.6) 55 (16.0) 0.92
General health 68 (20.1) 58 (16.9) 1.15
Mental health 57 (16.8) 46 (13.4) 1.14
Physical functioning 52 (15.3) 42 (12.2) 1.18
Role-emotional 73 (21.5) 69 (20.1) 1.02
Role-physical 75 (22.1) 62 (18.1) 1.19
Social functioning 32 (9.4) 42 (12.2) 0.68
Vitality 47 (13.9) 37 (10.8) 1.18
Time to deterioration HR (95%CI)*
Physical component summary 1.17 (0.82, 1.67)
Mental component summary 0.98 (0.70, 1.39)
32
OA06.04: Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC – Wu Y, et al
• Study objective
– To assess postoperative chemotherapy use and outcomes of adjuvant osimertinib in patients with resected
EGFR-mutant NSCLC
Wu Y, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.04
Primary endpoint
• DFS in stage II/IIIA patients
(investigator assessment)*
Secondary endpoints
• DFS in overall population*, DFS at 2, 3, 4,
and 5 years, OS, safety, HRQoL
R
1:1
PD/3 years/
discontinuation
PD/3 years/
discontinuation
Stratification
• Stage (IB vs. II vs. IIIA)
• EGFRm (Ex19del vs. L858R)
• Race (Asian vs. non-Asian)
Key patient inclusion criteria
• Completely resected stage IB,
II, IIIA NSCLC
• Confirmed EGFR mutation
(Ex19del/L858R)
• With or without adjuvant
chemotherapy
• WHO PS 0–1
(n=682)
Placebo QD
(n=343)
Osimertinib 80 mg QD
(n=339)
*Data previously reported
33
OA06.04: Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC – Wu Y, et al
• Key results
Wu Y, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.04
DFS in patients with adjuvant chemotherapy DFS in patients without adjuvant chemotherapy
Maturity 30%: Osimertinib 11%, placebo 50%
DFS events,
n (%)
Median DFS,
mo (95%CI) HR (95%CI)
Osimertinib (n=203) 22 (11) NR (38.8, NC) 0.16
(0.10, 0.26)Placebo (n=207) 103 (50) 22.1 (17.4, 32.9)
DF
S p
rob
ab
ility
1.0
0.8
0.6
0.4
0.2
0
Time from randomisation, months
4842363024181260
01144080121166190203
127244680119172207
No. at riskOsimertinib
Placebo
49%
89% 1.0
0.8
0.6
0.4
0.2
0
Time from randomisation, months
4842363024181260
0413345887106123136
111329426888115136
58%
89%
DFS events,
n (%)
Median DFS,
mo (95%CI) HR (95% CI)
Osimertinib (n=136) 15 (11) NR (NC, NC) 0.23
(0.13, 0.40)Placebo (n=136) 56 (41) 33.1 (22.6, NC)
Maturity 26%: Osimertinib 11%, placebo 41%
34
OA06.04: Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC – Wu Y, et al
• Key results (cont.)
• Conclusions
– In patients with resected EGFR-mutant NSCLC, adjuvant osimertinib demonstrated improvement in DFS in
those with or without adjuvant chemotherapy and irrespective of disease stage
Wu Y, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.04
Stage DFS
With adjuvant chemotherapy Without adjuvant chemotherapy
Osimertinib (n=28) Placebo (n=30) Osimertinib (n=78) Placebo (n=76)
IB Events, n (%) 4 (14) 11 (37) 7 (9) 18 (24)
Median, months (95%CI) NR (33.0, NC) 48.2 (21.0, 48.2) NR (NC, NC) NR (NC, NC)
HR (95%CI) NC (NC, NC) 0.38 (0.15, 0.88)
II Events, n (%) 6 (7) 36 (42) 5 (14) 16 (48)
Median, months (95%CI) NR (NC, NC) 29.4 (22.1, NC) NR (27.7, NC) 22.1 (10.8, NC)
HR (95%CI) 0.15 (0.06, 0.32) 0.20 (0.07, 0.52)
IIIA Events, n (%) 12 (13) 56 (61) 3 (14) 22 (81)
Median, months (95%CI) 38.8 (34.3, NC) 12.9 (10.9, 19.4) 38.6 (38.6, NC) 11.2 (8.2, 21.9)
HR (95%CI) 0.13 (0.06, 0.23) 0.10 (0.02, 0.29)
Advanced NSCLCNot radically treatable stage III and stage IV
First line
36
PS01.07: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutant NSCLC: First Disclosure of the Codebreak 100 Primary Analysis – Li BT, et al
• Study objective
– To assess the efficacy and safety of sotorasib, a KRAS G12C inhibitor, in patients with NSCLC harbouring a
KRAS p.G12C mutation
Li BT, et al et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.07
Sotorasib 960 mg/day PO
Key patient inclusion criteria
• Locally advanced or metastatic NSCLC
• KRAS p.G12C mutation
• Progressed on prior standard therapies
(n=126)
Primary endpoint
• ORR (BICR, RECIST v1.1)
Secondary endpoints
• DoR, DCR, TTR, PFS, OS, safety
PD
37
PS01.07: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutant NSCLC: First Disclosure of the Codebreak 100 Primary Analysis – Li BT, et al
• Key results
Li BT, et al et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.07
Progression-free survivalP
FS
1.0
0.8
0.6
0.4
0.2
0
Time, months
131211109876543210
0424313445495465757796119124No. at risk
mPFS: 6.8 months (95%CI 5.1, 8.2)
38
PS01.07: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutant NSCLC: First Disclosure of the Codebreak 100 Primary Analysis – Li BT, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC harbouring a KRAS p.G12C mutation, sotorasib demonstrated promising
activity and was generally well-tolerated
Li BT, et al et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.07
Grade 3 TRAEs, n (%) Sotorasib (n=126)
Any 25 (19.8)
Diarrhoea 5 (4.0)
ALT increased 6 (6.3)
AST increased 7 (5.6)
Blood alkaline phosphatase increased 1 (0.8)
Sotorasib (n=124)
ORR, % (95%CI) 37.1 (28.6, 46.2)
BOR, n (%)
CR 3 (2.4)
PR 43 (34.7)
SD 54 (43.5)
PD 20 (16.1)
NE/missing 4 (3.2)
DCR, % (95%CI) 80.6 (72.6, 87.2)
39Data cut-off: September 1, 2020. Median follow-up: 20.6 months
PS01.09: Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 – Boyer M, et al
• Study objective
– To assess the efficacy and safety of pembrolizumab + ipilimumab as a 1L therapy for patients with metastatic
NSCLC with PD-L1 TPS ≥50%
Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09
Co-primary endpoints
• OS and PFS (BICR, RECIST v1.1)
Secondary endpoints
• ORR, DoR, safety
R
1:1
Stratification
• ECOG PS (0 vs. 1)
• Region (East Asia vs. not East Asia)
• Histology (squamous vs. nonsquamous)
Key patient inclusion criteria
• Stage IV NSCLC
• PD-L1 TPS ≥50%
• No EGFR mutations or ALK
translocations
• No prior systemic therapy
• ECOG PS 0–1
(n=568)
Pembrolizumab 200 mg q3w (up to 35 doses) +
placebo (up to 18 doses)
(n=284)
Pembrolizumab 200 mg q3w (up to 35 doses) +
ipilimumab 1 mg/kg q6w (up to 18 doses)
(n=284)
40
PS01.09: Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 – Boyer M, et al
• Key results
*Nonbinding futility criteria met Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09
Events,
%
Median,
mo
(95%CI)
RMST at
24 mo,
mo
RMST at
max time,
mo
Pembro-Ipi 48.221.4
(16.6, NR)16.09 18.76
Pembro-Pbo 47.521.9
(18.0, NR)16.61 19.32
Overall survival
No. at risk Time, months
33302724211815129630
OS
, %
100
80
60
40
20
0
HR 1.08 (95%CI 0.85, 1.37); p=0.74
RMST difference at 24 mo: –0.52*
RMST difference at max observation time: –0.56*
12-month rate
63.6%
67.9%
00103762100146180204223245284Pembro-Ipi
02154177111154192215230252284Pembro-Pbo
41
PS01.09: Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 – Boyer M, et al
• Key results (cont.)
Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09
Events, % Median, mo (95%CI)
Pembro-Ipi 66.2 8.2 (6.0, 10.5)
Pembro-Pbo 64.8 8.4 (6.3, 10.5)
Progression-free survival
No. at risk Time, months
33302724211815129630
PF
S, %
100
80
60
40
20
0
HR 1.06 (95%CI 0.86, 1.30); p=0.72
12-month rate
41.3%
42.1%
001919366599117146189284Pembro-Ipi
01411204375104124157198284Pembro-Pbo
42
PS01.09: Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 – Boyer M, et al
• Key results (cont.)
Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09
Pembrolizumab + ipilimumab
(n=284)
Pembrolizumab + placebo
(n=284)
ORR, % (95%CI) 45.4 (39.5, 51.4) 45.4 (39.5, 51.4)
BOR, n (%)
CR 13 (4.6) 8 (2.8)
PR 116 (40.8) 121 (42.6)
SD 70 (24.6) 73 (25.7)
PD 51 (18.0) 44 (15.5)
NE 6 (2.1) 6 (2.1)
NA 28 (9.9) 32 (11.3)
Median DoR, mo (range) 16.1 (1.1+ to 26.0) 17.3 (2.0+ to 29.4+)
12-mo DoR rate, % 60.9 65.8
43
PS01.09: Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 – Boyer M, et al
• Key results (cont.)
• Conclusions
– In patients with metastatic NSCLC and PD-L1 TPS ≥50% with no EGFR or ALK aberrations, 1L
pembrolizumab + ipilimumab did not improve outcomes after a median follow-up of 20.6 months and had a
higher rate of toxicity than with pembrolizumab alone
Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09
AEs, n (%)
TRAEs irAEs
Pembrolizumab +
ipilimumab (n=282)
Pembrolizumab +
placebo (n=281)
Pembrolizumab +
ipilimumab (n=282)
Pembrolizumab +
placebo (n=281)
Any grade 215 (76.2) 192 (68.3) 126 (44.7) 91 (32.4)
Grade 3–5 99 (35.1) 55 (19.6) 57 (20.2) 22 (7.8)
Serious 78 (27.7) 39 (13.9) 54 (19.1) 20 (7.1)
Led to death 7 (2.5) 0 (0) 6 (2.1) 0 (0)
Led to discontinuation
Ipilimumab or placebo 17 (6.0) 9 (3.2) 5 (1.8) 3 (1.1)
Both drugs 54 (19.1) 21 (7.5) 34 (12.1) 12 (4.3)
44
OA01.03: Clinical Benefits of First-Line (1L) Cemiplimab Monotherapy by PD-L1 Expression Levels in Patients With Advanced NSCLC – Kilickap S, et al
• Study objective
– To assess the efficacy and safety of cemiplimab, a PD-1 inhibitor, as a 1L therapy for patients with
advanced NSCLC and PD-L1 expression of ≥50% in the EMPOWER-Lung 1 study
*Optional continuation of cemiplimab + chemotherapy (4 cycles); †optional crossover to cemiplimab monotherapy Kilickap S, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.03
Post-hoc analysis
• Clinical benefit by PD-L1 expression
(≥90%, >60% to <90% and ≥50% to ≤60%)
Cemiplimab 350 mg IV q3w*
(n=238)Key patient inclusion criteria
• Advanced NSCLC
• PD-L1 ≥50%
• No EGFR, ALK or ROS1 mutations
• Treatment naïve
• ECOG PS 0–1
(n=710)
Chemotherapy investigator choice†
(4–6 cycles)
(n=237)
R
1:1
Stratification
• Histology (squamous vs. nonsquamous)
• Region (Europe, Asia or RoW)
PD
PD
45
OA01.03: Clinical Benefits of First-Line (1L) Cemiplimab Monotherapy by PD-L1 Expression Levels in Patients With Advanced NSCLC – Kilickap S, et al
• Key results
Kilickap S, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.03
Overall survival
Pro
babili
ty o
f O
S
1.0
0.8
0.6
0.4
0.2
0
Time, months
181614121086420
Cemiplimab
PD-L1 ≥90%
PD-L1 >60 to <90%
PD-L1 ≥50 to ≤60%
Chemotherapy
PD-L1 ≥90%
PD-L1 >60 to <90%
PD-L1 ≥50 to ≤60%
mOS, months (95%CI)
HR (95%CI)
Cemiplimab
(n=238)
Chemotherapy
(n=237)
≥90% NR (13.4, NE) 13.3 (10.2, NE) 0.54 (0.27, 1.10)
>60 to <90% NR (NE, NE) 14.2 (9.6, 17.5) 0.49 (0.26, 0.92)
≥50 to ≤60% NR (13.2, NE) 11.7 (8.3, NE) 0.74 (0.44, 1.24)
mPFS, months (95%CI)
HR (95%CI)
Cemiplimab
(n=238)
Chemotherapy
(n=237)
≥90% 12.7 (9.8, 13.4) 6.1 (4.2, 6.2) 0.33 (0.19, 0.58)
>60 to <90% 6.2 (4.2, 8.4) 4.3 (4.1, 5.9) 0.57 (0.38, 0.85)
≥50 to ≤60% 4.3 (2.8, 5.2) 6.0 (4.4, 6.2) 0.89 (0.61, 1.29)
Progression-free survival
Pro
babili
ty o
f P
FS
1.0
0.8
0.6
0.4
0.2
0
Time, months
181614121086420
46
OA01.03: Clinical Benefits of First-Line (1L) Cemiplimab Monotherapy by PD-L1 Expression Levels in Patients With Advanced NSCLC – Kilickap S, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC and PD-L1 expression, cemiplimab demonstrated greater improvements in
survival and larger reductions in tumour volume in those with higher PD-L1 expression levels
Kilickap S, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.03
PD-L1 expression
tertile
ORR, % (95%CI)
Cemiplimab Chemotherapy
Overall ≥50% 35.3 (29.2, 41.7) 17.7 (13.1, 23.2)
≥50% to ≤60% 28.0 (18.7, 39.1) 21.4 (13.2, 31.7)
>60% to <90% 39.5 (28.4, 51.4) 16.7 (8.9, 27.3)
≥90% 38.8 (28.1, 50.3) 14.8 (7.9, 24.4)
Grade 3–5 TEAEs
occurring in ≥5%, n (%)
Cemiplimab
(n=355)
Chemotherapy
(n=342)
Any 132 (37.2) 166 (48.5)
Anaemia 12 (3.4) 56 (16.4)
Pneumonia 17 (4.8) 19 (5.6)
Thrombocytopenia 0 (0) 28 (8.2)
Neutropenia 2 (0.6) 35 (10.2)
Decreased neutrophil count 1 (0.3) 18 (5.3)
47
OA02.03: Pembrolizumab Plus Platinum Chemotherapy and Radiotherapy in Unresectable, Locally Advanced, Stage III NSCLC: KEYNOTE-799 – Reck M, et al
• Study objective
– To assess the efficacy and safety of pembrolizumab + concurrent chemoradiation therapy in patients with
locally advanced stage III NSCLC
*60 Gy in 30 daily 2-Gy fractions Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA02.03
Primary endpoints
• ORR (BICR, RECIST v1.1)
• Proportion developing grade ≥3 pneumonitis
Secondary endpoints
• PFS, OS, safety
Key patient inclusion criteria
• Stage IIIA-C, unresectable,
locally advanced NSCLC
• Treatment naïve
• ECOG PS 0–1
(n=216)
Pembrolizumab 200 mg +
pemetrexed 500 mg/m2 +
cisplatin 75 mg/m2 q3w
Pembrolizumab 200 mg +
paclitaxel 200 mg/m2 +
carboplatin AUC6 q3w
Cohort A: Squamous and nonsquamous NSCLC (n=112)
Cohort B: Nonsquamous NSCLC (n=101)
Pembrolizumab 200 mg +
pemetrexed 500 mg/m2 +
cisplatin 75 mg/m2 q3w +
thoracic radiotherapy*
Pembrolizumab 200 mg +
paclitaxel 45 mg/m2 +
carboplatin AUC2 q3w +
thoracic radiotherapy*
Pembrolizumab
200 mg q3w
Pembrolizumab
200 mg q3w
Cycle 1 Cycle 2–3 Cycle 4–17
48
OA02.03: Pembrolizumab Plus Platinum Chemotherapy and Radiotherapy in Unresectable, Locally Advanced, Stage III NSCLC: KEYNOTE-799 – Reck M, et al
• Key results
Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA02.03
Progression-free
survival
Overall
survival
Cohort A: Squamous and nonsquamous NSCLC
Time, months211815129630
PF
S,
%
100
80
60
40
20
0
n
112
Median (95%CI)
NR (16.6, NR)
12-month rate
67.7%
023053688193112No. at risk
Cohort B: Nonsquamous only
Time, months
PF
S,
%
100
80
60
40
20
0
n
61
Median (95%CI)
NR (10.6, NR)
12-month rate
65.2%
1815129630
092037445261No. at risk
Time, months211815129630
OS
, %
100
80
60
40
20
0
n
112
Median (95%CI)
NR (NR, NR)
12-month rate
81.2%
0850839498106112No. at riskTime, months
211815129630
OS
, %
100
80
60
40
20
0
n
61
Median (95%CI)
NR (NR, NR)
12-month rate
88.0%
06153756596161No. at risk
49
OA02.03: Pembrolizumab Plus Platinum Chemotherapy and Radiotherapy in Unresectable, Locally Advanced, Stage III NSCLC: KEYNOTE-799 – Reck M, et al
• Key results (cont.)
• Conclusions
– In patients with unresectable, locally advanced stage III NSCLC, adding pembrolizumab to concurrent
chemoradiation continued to demonstrate encouraging antitumor activity and the safety profile was
consistent with those of the established profiles
Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA02.03
Cohort A (n=112) Cohort B (n=61)
ORR, n (%) [95%CI] 78 (69.6) [60.2, 78.0] 43 (70.5) [57.4, 81.5]
BOR, n (%)
CR 4 (3.6) 3 (4.9)
PR 74 (66.1) 40 (65.6)
SD 21 (18.8) 12 (19.7)
PD 1 (0.9) 0 (0)
NE 2 (1.8) 0 (0)
NA 10 (8.9) 6 (9.8)
Median DoR, mo (range) NR (1.4+ to 16.1+) NR (2.0+ to 15.9+)
AEs Cohort A (n=112) Cohort B (n=61)
Grade ≥3 pneumonitis, n (%) [95%CI] 9 (8.0) [3.7, 14.7] 8 (7.9) [3.5, 15.0]
TRAE, n (%) 105 (93.8) 96 (95.0)
Grade 3–5 72 (64.3) 47 (46.5)
Led to death 4 (3.6) 1 (1.0)
Led to discontinuation of any component 38 (33.9) 16 (15.8)
Pembrolizumab 27 (24.1) 15 (14.9)
Radiotherapy 2 (1.8) 0 (0)
Chemotherapy 18 (16.1) 3 (3.0)
Immune-mediated & infusion reactions 59 (52.7) 36 (35.6)
Grade 3–5 18 (16.1) 10 (9.9)
Led to death 4 (3.6) 1 (1.0)
50
OA07.09: Sintilimab in Combination with Anlotinib as First-Line Therapy for Advanced NSCLC: Final Analysis of Primary Endpoints – Han B, et al
• Study objective
– To assess the efficacy and safety of sintilimab, a PD-1 inhibitor, + anlotinib, an anti-angiogenesis multikinase
inhibitor, as a 1L therapy for patients with advanced NSCLC
Han B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.09
Sintilimab 200 mg IV D1 +
anlotinib 12 mg PO D1–14 q3w
Key patient inclusion criteria
• Stage IIIB–IV NSCLC
• No driver gene (EGFR, ALK, ROS1)
• Treatment naïve
• ECOG PS 0–1
(n=22)
Primary endpoints
• ORR, safety
Secondary endpoints
• DCR, PFS, OS
PD/toxicity
51
OA07.09: Sintilimab in Combination with Anlotinib as First-Line Therapy for Advanced NSCLC: Final Analysis of Primary Endpoints – Han B, et al
• Key results
Median follow-up: 15.8 months (range 8.3–19.3)
Data cut-off: April 30, 2020 Han B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.09
Progression-free survival
Su
rviv
al p
rob
ab
ility
, %
100
75
50
25
0
181614121086420
0 (13)1 (12)4 (10)9 (7)15 (1)16 (1)19 (1)21 (1)22 (0)22 (0)
Time, months
Sintilimab
Patient subgroups
mPFS,
mo (95%CI)
12-mo PFS,
% (95%CI)
ITT (n=22) 15 (8.3, NR) 71.4 (47.2, 86.0)
Nonsquamous (n=9) NR (4.3, NR) 66.7 (28.2, 87.8)
Squamous (n=12) 13 (7.7, NR) 72.7 (37.1, 90.3)
PD-L1+ (n=13) NR (7.7, NR) 76.9 (44.2, 91.9)
PD-L1– (n=8) 14 (4.5, 15) 62.5 (22.9, 86.1)
TMB ≥10 (n=6) NR (NR, NR) 100 (100, 100)
TMB <10 (n=10) 14 (4.3, 15) 60.0 (25.3, 82.7)
No. at risk (no. censored)
52
OA07.09: Sintilimab in Combination with Anlotinib as First-Line Therapy for Advanced NSCLC: Final Analysis of Primary Endpoints – Han B, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC, 1L sintilimab + anlotinib demonstrated encouraging activity and was
generally well-tolerated
Han B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.09
Response and duration n=22
ORR, % (95%CI) 72.7 (49.8, 89.3)
BOR, n (%)
CR 0 (0)
PR 16 (72.7)
SD 6 (27.3)
DCR, % (95%CI) 100 (84.6, 100)
Median TTR, mo (95%CI) 1.6 (1.4, 2.9)
Median DoR, mo (95%CI) NR (3.2, NC)
AE, n (%) n=22
Any TRAE 22 (100)
Grade ≥3 TRAEs 12 (54.4)
Grade ≥3 irAEs 1 (4.5)
Led to anlotinib dose reduction 5 (22.7)
Led to discontinuation
Both drugs 1 (4.5)
Sintilimab 1 (4.5)
Anlotinib 1 (4.5)
Grade 3 TRAE, n (%) n=22
Hypertension 2 (9.1)
Rash 1 (4.5)
Hand-foot skin reaction 1 (4.5)
53
MA11.05: Tepotinib in Patients with MET exon 14 (METex14) Skipping Advanced NSCLC: Updated Efficacy Results from VISION Cohort A – Paik PK, et al
• Study objective
– To assess the updated efficacy and safety of tepotinib in patients with advanced NSCLC and MET exon 14
skipping mutation who had at least 9 months of follow-up
Paik PK, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.05
Tepotinib 500 mg/day PO
(n=152)
Key patient inclusion criteria
• Advanced NSCLC
• MET exon 14 skipping mutation
• EGFR or ALK WT
(n=255)
Primary endpoint
• ORR (RECIST v1.1)
Secondary endpoints
• DoR, safety
54
MA11.05: Tepotinib in Patients with MET exon 14 (METex14) Skipping Advanced NSCLC: Updated Efficacy Results from VISION Cohort A – Paik PK, et al
• Key results
Data cut-off: July 1, 2020 Paik PK, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.05
Efficacy
according to
IRC
Treatment-
naïve
(n=69)
Previously
treated
(n=83)
Overall
(N=152)
ORR, %
(95%CI)
44.9
(32.9, 57.4)
44.6
(33.7, 55.9)
44.7
(36.7, 53.0)
BOR, n (%)
CR 0 0 0
PR 31 (44.9) 37 (44.6) 68 (44.7)
SD 16 (23.2) 23 (27.7) 39 (25.7)
PD 13 (18.8) 13 (15.7) 26 (17.1)
NE 9 (13.0) 10 (12.0) 19 (12.5)
Median DoR, mo
(95%CI)
10.8
(6.9, NE)
11.1
(9.5, 18.5)
11.1
(8.4, 18.5)
Median PFS, mo
(95%CI)
8.5
(6.8, 11.3)
10.9
(8.2, 12.7)
8.9
(8.2, 11.2)
N ORR (95%CI) by IRC
Overall
Treatment-naïve
Previously treated
Platinum-based CT
Also received IO
As combination
As single agent in
a separate line
152
69
83
74
29
10
20
44.7 (36.7, 53.0)
44.9 (32.9, 57.4)
44.6 (33.7, 55.9)
48.6 (36.9, 60.6)
41.4 (23.5, 61.1)
40.0 (12.2, 73.8)
40.0 (19.1, 63.9)
0 20 40 60 80 100
ORR, % and 95%CI
55
MA11.05: Tepotinib in Patients with MET exon 14 (METex14) Skipping Advanced NSCLC: Updated Efficacy Results from VISION Cohort A – Paik PK, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC and MET exon 14 skipping mutations, tepotinib demonstrated encouraging
activity across all therapy lines and had a manageable safety profile
Paik PK, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.05
TRAEs, n (%)
Treatment-
naïve
(n=125)
Previously
treated
(n=130)
Prior IO
(n=66)
Overall
(N=255)
Any 109 (87) 111 (85) 55 (83) 220 (86)
Grade ≥3 39 (31) 25 (19) 12 (18) 64 (25)
Led to dose reduction 39 (31) 32 (25) 15 (23) 71 (28)
Led to interruption 50 (40) 40 (31) 22 (33) 90 (35)
Led to discontinuation 19 (15) 8 (6) 5 (8) 27 (11)
TRAEs occurring in ≥10%
of all patients, n (%)
Treatment-
naïve
(n=125)
Previously
treated
(n=130)
Prior IO
(n=66)
Overall
(N=255)
Peripheral oedema 73 (58) 65 (50) 30 (45) 138 (54)
Nausea 30 (24) 21 (16) 8 (12) 51 (20)
Diarrhoea 26 (21) 24 (18) 9 (14) 50 (20)
Blood creatinine increased 23 (18) 22 (17) 13 (20) 45 (18)
Hypoalbuminemia 21 (17) 16 (12) 9 (14) 37 (15)
Advanced NSCLCNot radically treatable stage III and stage IV
Later lines
57
OA01.06: Randomised Phase 2 Study of Nivolumab (N) Versus Nivolumab and Ipilimumab (NI) Combination in EGFR Mutant NSCLC – Lai GG, et al
• Study objective
– To assess the efficacy and safety of nivolumab with or without ipilimumab in patients with EGFR-mutant
NSCLC
*Enrolment was terminated early due to futility Lai GG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.06
Primary endpoint
• ORR
Secondary endpoint
• Safety
R
1:1
Crossover
permitted
Stratification
• PD-L1 status
• Presence of brain metastasis
Key patient inclusion criteria
• Advanced NSCLC
• EGFR mutant
• Failed 1 line of standard EGFR TKI
(n=31*)Nivolumab
(n=15)
Nivolumab + ipilimumab
(n=16)
58
OA01.06: Randomised Phase 2 Study of Nivolumab (N) Versus Nivolumab and Ipilimumab (NI) Combination in EGFR Mutant NSCLC – Lai GG, et al
• Key results
Lai GG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.06
Progression-free survivalBest overall response
-30
-10
10
30
50
70
90
110
130
150
Nivo + Ipi
Nivo
Nivo + Ipi, n (%) Nivo, n (%) Total (%)
PR 1 (6.3) 0 (0) 1 (8.2)
SD 6 (37.5) 6 (40.0) 12 (38.7)
PD 9 (56.8) 8 (53.3) 17 (54.8)
*1 not evaluable†Clinical PD
* †
% c
ha
ng
e in
tu
mo
ur
siz
e r
ela
tive
to
ba
se
line
9 23 6 27 21 26 3 20 8 30 11 29 19 12 2817 31 13 25 1 4 18 14 10 15 24 16 2 5 7Patient number
121086420
Su
rviv
al p
rob
ab
ility
1.00
0.75
0.50
0.25
0
Time from start of treatment, monthsNo. at risk
01112515
02223516
Nivo
Nivo + Ipi
mPFS,
mo (95%CI)
6-mo PFS rate,
% (95%CI)
Nivo + Ipi 1.22 (1.15, NE) 8.9 (1.5, 54.4)
Nivo 1.31 (1.22, NE) 8.3 (1.3, 52.6)
Overall 1.31 (1.15, 2.53) 9.0 (2.5, 31.8)
p=0.87
59
OA01.06: Randomised Phase 2 Study of Nivolumab (N) Versus Nivolumab and Ipilimumab (NI) Combination in EGFR Mutant NSCLC – Lai GG, et al
• Key results (cont.)
• Conclusions
– In patients with pretreated EGFR-mutant NSCLC, neither nivolumab alone nor nivolumab + ipilimumab
demonstrated any significant clinical benefit
Lai GG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.06
AEs, n (%) Any grade Grade 3
Any 23 (74.2) 2 (6.0)
Immune-related
Skin 11 (35.5) -
Endocrine 4 (12.9) 1 (3.2)
Gastrointestinal 3 (9.6) -
Hepatic 3 (9.6) -
Pulmonary 1 (3.2) -
Musculoskeletal - 1 (3.2)
60
OA01.07: A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC – Krebs MG, et al
• Study objective
– To assess the efficacy and safety of bemcentinib, an AXL inhibitor, + pembrolizumab in patients with
advanced NSCLC
Krebs MG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.07
Primary endpoint
• ORR (RECIST v1.1)
Secondary endpoints
• DCR, PFS, OS, safety
Cohort C: Post-chemo-CPI (n=29)
Progressing on platinum-doublet chemotherapy
+ pembrolizumab
Cohort B: Post-CPI (n=29)
Progressing on prior CPI
Cohort A: Post-chemo (n=48)
Failed chemotherapy, IO naive
Key patient inclusion criteria
• Stage IV lung adenocarcinoma
• Previously treated
(n=106)
Bemcentinib 200 mg/day
+ pembrolizumab 200 mg
q3w
61
OA01.07: A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC – Krebs MG, et al
• Key results
Krebs MG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.07
Cohort BCohort A
cAXL+ve (n=7) cAXL-ve (n=7)
mPFS, mo 4.73 1.87
HR (95%CI); p-value 0.22 (0.04, 1.26); 0.066
ORR, n (%) 1 (14) 6 (86)
CBR, n (%) 0 (0) 2 (29)
cAXL+ve (n=15) cAXL-ve (n=15)
mPFS, mo 8.4 1.9
mOS, mo 17.3 12.4
ORR, n (%) 5 (33) 11 (73)
CBR, n (%) 1 (7) 6 (40)
PF
S p
rob
ab
ility
1.00
0.75
0.50
0.25
0
Time, months24211815129630
Median:
8.4 mo
Median:
1.9 mop=0.031
PF
S p
robabili
ty
1.00
0.75
0.50
0.25
0
Time, months
Median:
4.73 moMedian:
1.87 mo
p=0.031
109876543210
HR 0.22 (95%CI 0.04, 1.26)
p=0.066cAXL positive
cAXL negative cAXL positive
cAXL negative
62
OA01.07: A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC – Krebs MG, et al
• Key results (cont.)
• Conclusions
– In pretreated patients with advanced NSCLC who were cAXL+, bemcentinib + pembrolizumab demonstrated
clinical activity and was generally well-tolerated
– Results for progression after chemo-immunotherapy are expectedKrebs MG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.07
TRAEs occurring in ≥10% (n=75), n (%) Any grade Grade ≥3
ALT increased 25 (33) 9 (12)
AST increased 24 (32) 6 (8)
Diarrhoea 24 (32) 1 (1)
Asthenia 14 (19) 4 (5)
Pruritus 12 (16) 0 (0)
Nausea 11 (15) 0 (0)
Blood creatinine increased 10 (13) 0 (0)
ECG QT prolonged 10 (13) 1 (1)
Fatigue 10 (13) 1 (1)
Anaemia 9 (12) 2 (3)
Appetite decreased 8 (11) 0 (0)
63
OA03.03: Datopotamab Deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in Patients With Advanced NSCLC: Updated Results of TROPION-PanTumor01 Phase 1 Study – Spira AI, et al
• Study objective
– To assess the efficacy and safety of datopotamab deruxtecan, a TROP2 ADC, in patients with advanced or
metastatic NSCLC
Spira AI, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.03
Primary endpoints
• MTD, safety
Secondary endpoints
• Efficacy, PK
Datopotamab deruxtecan 4 mg/kg
(n=50)
Datopotamab deruxtecan 6 mg/kg
(n=45)
Datopotamab deruxtecan 8 mg/kg
(n=80)Key patient inclusion criteria
• Advanced or metastatic NSCLC
• Refractory to or relapsed on
standard treatment
• Tumour tissue available
(n=175)
64
OA03.03: Datopotamab Deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in Patients With Advanced NSCLC: Updated Results of TROPION-PanTumor01 Phase 1 Study – Spira AI, et al
• Key results
– mPFS (95%CI): 4 mg/kg: 4.3 mo (2.0, NE); 6 mg/kg: 8.2 mo (1.5, 11.8); 8 mg/kg: 5.4 mo (4.1, 7.1)
Spira AI, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.03
Best change in sum of diameters and overall response (BICR)
Best perc
ent
change in
SoD
from
baselin
e, %
80
60
40
20
0
–20
–40
–60
–80
–100
Dato-DXd
dose
Response-
evaluable
patients, n
Confirmed
CR/PR, n
CR/PR (too
early to be
confirmed), n
ORR,
n (%)
DCR,
n (%)
PD,
n (%)
4 mg/kg 40 7 2 9 (23) 29 (73) 6 (15)
6 mg/kg 39 6 2 9 (21) 26 (67) 8 (21)
8 mg/kg 80 19 1 20 (25) 64 (80) 7 (9)
Dato-DXd dose
4 mg/kg
6 mg/kg
8 mg/kg
65
OA03.03: Datopotamab Deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in Patients With Advanced NSCLC: Updated Results of TROPION-PanTumor01 Phase 1 Study – Spira AI, et al
• Key results (cont.)
• Conclusions
– In heavily pretreated patients with advanced NSCLC, datopotamab deruxtecan provided promising antitumor
activity with a manageable safety profile
Spira AI, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.03
AEs, n (%) Dato-DXd 8 mg/kg (n=80) Dato-DXd 6 mg/kg (n=80) Dato-DXd 4 mg/kg (n=80)
TEAE 79 (99) 41 (91) 48 (96)
Grade ≥3 45 (56) 17 (38) 11 (22)
TRAE 76 (95) 35 (78) 43 (86)
Grade ≥3 27 (34) 7 (16) 5 (10)
Serious TEAE 38 (48) 16 (36) 9 (18)
Treatment related 16 (20) 4 (9) 4 (8)
TEAE led to death 7 (9) 1 (2) 4 (8)
Treatment related 2 (3) 0 (0) 1 (2)
66
OA03.04: Efficacy and Safety of the Novel HER3 Directed Antibody Drug Conjugate Patritumab Deruxtecan (HER3-DXd; U3-1402) in EGFR-mutated NSCLC – Yu H, et al
• Study objective
– To assess the safety and activity of patritumab deruxtecan, a novel HER3-directed ADC, in pretreated
patients with advanced T790M– EGFR-mutant NSCLC
Yu H, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.04
Primary endpoint
• ORR (BICR)
Secondary endpoint
• Safety
Patritumab deruxtecan
5.6 mg/kg q3w
(n=12)
Key patient inclusion criteria
• Metastatic/unresectable NSCLC
• EGFR mutation
• Progression on osimertinib or
after progression on erlotinib,
gefitinib or afatinib in T790M–
(n=57)
Dose escalation
(3.2 mg/kg–6.4 mg/kg)
Dose expansion
Cohort 1
Patritumab deruxtecan
5.6 mg/kg q3w
Adenocarcinoma and
treated ≥EGFR TKI
and ≥prior platinum
(n=45)
67
OA03.04: Efficacy and Safety of the Novel HER3 Directed Antibody Drug Conjugate Patritumab Deruxtecan (HER3-DXd; U3-1402) in EGFR-mutated NSCLC – Yu H, et al
• Key results
Yu H, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.04
Activity according to BICR evaluation
(efficacy-evaluable population)
1514131211109876543210
Treatment duration, months
CR
PR
SD
PD
Treatment ongoing (27 of 56 patients [48%])
Treatment ongoing after progression
Confirmed BOR, n (%) n=56
Confirmed ORR, n (%) [95%CI] 14 (25) [14.4, 38.4]
Confirmed BOR, n (%)
CR 1 (2)
PR 13 (23)
SD 25 (45)
PD 9 (16)
NE 8 (14)
DCR, n (%) [95%CI] 39 (70) [55.9, 81.2]
Median TTR, months (range) 2.0 (1.2–2.8)
Median DoR, months (range) 6.9 (3.0–7.0)
68
OA03.04: Efficacy and Safety of the Novel HER3 Directed Antibody Drug Conjugate Patritumab Deruxtecan (HER3-DXd; U3-1402) in EGFR-mutated NSCLC – Yu H, et al
• Key results (cont.)
• Conclusions
– In heavily pretreated patients with T790M– EGFR-mutant NSCLC, patritumab deruxtecan demonstrated
early promising antitumor activity and had a manageable safety profile
Yu H, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.04
TEAEs occurring in ≥20% of patients (n=57), n (%) Any grade Grade ≥3
Fatigue 33 (58) 5 (9)
Nausea 31 (54) 2 (4)
Thrombocytopenia 30 (53) 16 (28)
Appetite decreased 20 (35) 1 (2)
Neutropenia 19 (33) 11 (19)
Vomiting 17 (30) 1 (2)
Alopecia 17 (30) -
Anaemia 15 (26) 5 (9)
Constipation 14 (25) 0 (0)
AEs, n (%) n=57
TEAE 57 (100)
Grade ≥3 38 (67)
Led to discontinuation 5 (9)
Led to dose reduction 10 (18)
Led to dose interruption 17 (30)
Led to death 3 (5)
Serious TEAE 21 (37)
Grade ≥3 18 (32)
Treatment related 11 (19)
69
OA04.03: Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations – Zhou C, et al
• Study objective
– To assess the efficacy and safety of mobocertinib, a TKI targeting EGFR exon 20 in-frame insertion
mutations, in patients with NSCLC and EGFR exon 20 insertions
Zhou C, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.03
Primary endpoint
• ORR (ICR, RECIST v1.1)
Secondary endpoints
• TTR, DCR, DoR, PFS, safety
Mobocertinib
(n=28; 22 prior platinum)
Key patient inclusion criteria
• Locally advanced or metastatic
NSCLC
• EGFR exon20 insertion
mutation
• ≥1 prior line of therapy
• ECOG PS 0–1
Dose escalation/expansion
Mobocertinib 160 mg/day PO
(n=96; 86 prior platinum)
EXCLAIM Extension cohort
70
OA04.03: Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations – Zhou C, et al
• Key results
Zhou C, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.03
Platinum-pretreated cohort (n=114) EXCLAIM cohort (n=96)
Pro
babili
ty o
f P
FS
1.0
0.8
0.6
0.4
0.2
0
242220181614121086420
02455681118426484114
Time, months
Pro
babili
ty o
f P
FS
1.0
0.8
0.6
0.4
0.2
0
121086420
131033537196
Time, months
Censored
Number of events: 44
Median: 7.3
Min, Max: 0.0, 12.0
Number of events: 56
Median: 7.3
Min, Max: 0.0, 24.0
Censored
Progression-free survival
No. at risk
71
OA04.03: Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations – Zhou C, et al
• Key results (cont.)
• Conclusions
– In patients with NSCLC and EGFR exon 20 insertions, mobocertinib demonstrated clinical activity with a RR
of 23% in the EXCLAIM extension cohort
Zhou C, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.03
Platinum-pretreated
cohort (n=114)
EXCLAIM cohort
(n=96)
Median time on treatment, mo (range) 7.0 (0–31) 6.5 (0–14)
ORR per IRC, n (%) [95%CI] 30 (26) [19, 35] 22 (23) [15, 33]
ORR per investigator, n (%) [95%CI] 40 (35) [26, 45] 31 (32) [23, 43]
DoR per IRC, mo (95%CI) 17.5 (8.3, NE) NE (8.3, NE)
DoR per investigator, mo (95%CI) 13.9 (5.6, NE) NE (5.5, NE)
DCR per IRC, n (%) [95%CI] 89 (78) [69, 85] 73 (76) [66, 84]
DCR per investigator, n (%) [95%CI] 89 (78) [69, 85] 72 (75) [65, 83]
AEs, n (%)
Platinum-pretreated
cohort (n=114)
EXCLAIM cohort
(n=96)
Any TRAE 113 (99) 95 (99)
Grade ≥3 TRAE 53 (46) 39 (41)
Serious TEAE 52 (46) 39 (41)
AE led to dose reduction 28 (25) 20 (21)
AE led to treatment discontinuation 19 (17) 10 (10)
TRAE led to death 1 (1) 1 (1)
72
OA04.04: Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer – Sabari JK, et al
• Study objective
– To assess the efficacy and safety of amivantamab, an EGFR-MET bispecific antibody, in a cohort of patients
with NSCLC and EGFR exon 20 insertion mutation who had progressed on prior platinum-based
chemotherapy in the CHRYSALIS study
*1400 mg for ≥80 kg Sabari JK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.04
Primary endpoint
• ORR (investigator assessed, RECIST v1.1)
Secondary endpoints
• CBR, DoR, PFS, OS, safety
Amivantamab 1050 mg*
(n=81)
Key patient inclusion criteria
• Unresectable or metastatic NSCLC
• EGFR exon 20 insertion mutation
• Progressed on platinum-based
chemotherapy
(n=114)
73
OA04.04: Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer – Sabari JK, et al
• Key results
Sabari JK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.04
Best overall responseAmivantamab: Efficacy by BICR
BICR-assessed response Efficacy population (n=81)
ORR, % (95%CI) 40 (29, 51)
BOR, n (%)
CR 3 (4)
PR 29 (36)
SD 39 (48)
PD 8 (10)
NE 1 (1)
Median DoR, mo (95%CI) 11.1 (6.9, NR)
CBR, % (95%CI) 74 (63, 83)
mPFS, mo (95%CI) 8.3 (6.5, 10.9)
mOS, mo (95%CI) 22.8 (14.6, NR)
Median follow-up: 9.7 mo (range 1.1–29.3)
Overall
Age, years
<65 years
≥65 years
Sex
Male
Female
Race
Asian
Non-Asian
Baseline ECOG PS
0
≥1
Prior lines of therapy
1
2
≥3
History of smoking
Yes
No
History of brain metastases
Yes
No
n/N ORR, % (95%CI)ORR, %
32/81
21/48
11/33
15/33
17/48
17/40
14/32
14/26
18/55
10/31
7/24
15/26
13/38
19/43
7/18
25/63
40 (29, 51)
44 (30, 59)
33 (18, 52)
46 (28, 64)
35 (22, 51)
43 (27, 59)
44 (26, 62)
54 (33, 73)
33 (21, 47)
32 (17, 51)
29 (13, 51)
58 (37, 77)
34 (20, 51)
44 (29, 60)
39 (17, 64)
40 (28, 53)
100806040200
74
OA04.04: Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer – Sabari JK, et al
• Key results (cont.)
• Conclusions
– In previously platinum-treated patients with NSCLC and EGFR exon 20 insertion mutation, amivantamab
demonstrated encouraging activity and was generally well-tolerated
Sabari JK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.04
BOR by insertion region ORR, % CBR, %
Helical (n=1) 100 100
Near loop (n=54) 41 70
Far loop (n=8) 25 75
Not detected by ctDNA (n=18) 39 83
TRAEs, n (%) Safety population (n=114)
Any 112 (98)
Grade ≥3 18 (16)
Serious 10 (9)
Led to discontinuation 5 (4)
Led to dose reduction 15 (13)
Led to dose interruption 24 (21)
75
OA04.05: Trastuzumab Deruxtecan in HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Interim Results of DESTINY-Lung01 – Nakagawa K, et al
• Study objective
– To assess the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-overexpressing
metastatic NSCLC
*Data previously presented at ASCO 2020 Nakagawa K, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.05
Primary endpoint
• ORR (ICR)
Secondary endpoints
• DCR, DoR, PFS, OS, safety
Cohort 1:
HER2 expressing (IHC3+ or IHC2+)
T-Dxd 6.4 mg/kg q3w
(n=49)
Key patient inclusion criteria
• Unresectable/metastatic
nonsquamous NSCLC
• Relapsed/refectory to standard
treatment
• HER2 expressing or HER2-
activating mutation
• No prior HER2-targeted therapy
Cohort 2*:
HER2 mutated
T-Dxd 6.4 mg/kg q3w
(n=42)
76
OA04.05: Trastuzumab Deruxtecan in HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Interim Results of DESTINY-Lung01 – Nakagawa K, et al
• Key results
Nakagawa K, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.05
PFS (n=49) OS (n=49)
mPFS 5.4 mo (95%CI 2.8, 7.0) mOS 11.3 mo (95%CI 7.8 NE)
Time, months
PF
S p
robabili
ty
1.0
0.8
0.6
0.4
0.2
0
131211109876543210
022235710172326294549No. at risk
Upper & lower 95%CI
Censored
Time, months
OS
pro
babili
ty
1.0
0.8
0.6
0.4
0.2
0
Upper & lower 95%CI
Censored
131211109876543210 191817161514
47111316202327334142444549 022234
77
OA04.05: Trastuzumab Deruxtecan in HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Interim Results of DESTINY-Lung01 – Nakagawa K, et al
• Key results (cont.)
• Conclusions
– In heavily pretreated patients with metastatic HER2-overexpressing (IHC 2+/3+) NSCLC, trastuzumab
deruxtecan demonstrated promising activity and the safety profile was generally comparable to previous
findings
Nakagawa K, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.05
IHC 3+ (n=10) IHC 2+ (n=39) Overall (n=49)
ORR, n (%) [95%CI] 2 (20.0) [2.5, 55.6] 10 (25.6) [13.0, 42.1] 12 (24.5) [13.3, 38.9]
BOR, n (%)
CR 0 (0) 1 (2.6) 1 (2.0)
PR 2 (20.0) 9 (23.1) 11 (22.4)
SD 6 (60.0) 16 (41.0) 22 (44.9)
PD 1 (10.0) 10 (25.6) 11 (22.4)
NE 1 (10.0) 3 (7.7) 4 (8.2)
DCR, n (%) [95%CI] 8 (80.0) [44.4, 97.5] 26 (66.7) [49.8, 80.9] 34 (69.4) [54.6, 81.8]
Median DoR, mo (95%CI) 6.0 (NE, NE) 5.8 (3.2, NE) 6.0 (3.2, NE)
TRAEs, n (%) n=49
Any 44 (89.8)
Grade ≥3 27 (55.1)
Serious 8 (16.3)
Led to dose discontinuation 6 (12.2)
Led to dose reduction 16 (32.7)
Led to dose interruption 17 (34.7)
78
OA04.06: Neratinib in Pretreated EGFR Exon 18-Mutant Non-Small Cell Lung Cancer (NSCLC): Initial Findings From the SUMMIT Basket Trial – Boni V, et al
• Study objective
– To assess the efficacy and safety of neratinib in a cohort of patients with NSCLC and EGFR exon 18 mutation
*Prophylaxis with loperamide (first 6 weeks, then PRN) mandatory Boni V, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.06
Primary endpoint
• ORR (RECIST v1.1)
Secondary endpoints
• DoR, CBR, PFS, safety
Neratinib 240 mg/day PO*
Key patient inclusion criteria
• Lung cancer
• EGFR exon 18 mutation
• Treatment naïve or previously
treated with EGFR or pan-HER TKIs
• Prior chemotherapy and/or
checkpoint inhibitors permitted
• ECOG PS 0–2
(n=11)
79
OA04.06: Neratinib in Pretreated EGFR Exon 18-Mutant Non-Small Cell Lung Cancer (NSCLC): Initial Findings From the SUMMIT Basket Trial – Boni V, et al
• Key results
Boni V, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.06
Efficacy evaluable (n=11) TKI pretreated (n=10)
Confirmed ORR, % (95%CI) 36 (11, 69) 40 (12, 74)
CR, n 0 0
PR, n 4 4
BOR, % (95%CI) 54 (23, 83) 60 (26, 88)
CR, n 0 0
PR, n 6 6
Median DoR, mo (95%CI) 7.5 (4.0, NE) 7.5 (4.0, NE)
CBR, % (95%CI) 73 (39, 94) 80 (44, 97)
CR or PR, n 4 4
SD ≥16 weeks, n 4 4
mPFS, mo (95%CI) 6.9 (2.1, NA) 9.1 (3.7, NA)
80
OA04.06: Neratinib in Pretreated EGFR Exon 18-Mutant Non-Small Cell Lung Cancer (NSCLC): Initial Findings From the SUMMIT Basket Trial – Boni V, et al
• Key results (cont.)
• Conclusions
– In pretreated patients with NSCLC and EGFR exon 18 mutation, neratinib demonstrated promising early
clinical activity and was generally well-tolerated
Boni V, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.06
TEAEs, n (%) Any grade Grade ≥3
Diarrhoea 5 (45.5) 0 (0)
Vomiting 4 (36.4) 0 (0)
Constipation 3 (27.3) 0 (0)
Nausea 3 (27.3) 0 (0)
Appetite decreased 3 (27.3) 1 (9.1)
Dizziness 2 (18.2) 0 (0)
Hypertension 2 (18.2) 0 (0)
Dry mouth 2 (18.2) 0 (0)
Fatigue 2 (18.2) 0 (0)
81
MA11.07: Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors – Cho BC, et al
• Study objective
– To assess the efficacy and safety of repotrectinib in patients with ROS1 or NTRK mutated advanced solid
tumours
Cho BC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.07
Primary endpoint
• ORR (BICR, RECIST v1.1)
Secondary endpoints
• DoR, PFS, safety
Cohort 2: ROS1+ NSCLC (n=60)
1 prior ROS1 TKI and 1 platinum-based chemotherapy
Cohort 3: ROS1+ NSCLC (n=40)
2 prior ROS1 TKI and no prior chemotherapy
Cohort 1: ROS1+ NSCLC (n=55)
ROS1 TKI-naïve
Key patient inclusion criteria
• Advanced solid tumours
• ROS1 or NTRK1/2/3 fusion
(n=185)
Cohort 4: ROS1+ NSCLC (n=60)
1 prior ROS1 TKI and no prior chemotherapy
Repotrectinib
160 mg/day
for 14 days
followed by
160 mg BIDCohort 5: NTRK+ advanced solid tumours (n=55)
TRK TKI-naïve
Cohort 6: NTRK+ advanced solid tumours (n=40)
TRK TKI-pretreated
82
MA11.07: Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors – Cho BC, et al
• Key results
Cho BC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.07
Overall response (n=22)
Phase 2
(n=15)
Phase 1 + 2
(n=22)
Confirmed ORR, % (95%CI) 93 (68, 100) 91 (71, 99)
N=22 patients with baseline and at least two post
baseline scans
• n=15 Phase 2 patients
• n=7 Phase 1 patients treated at or above the
Phase 2 recommended dose
As of 31 Dec 2020, the 16th patient in Phase 2 has an
unconfirmed PR and is on treatment awaiting a second
post-baseline confirmatory scan
Max.
% c
hange in b
aselin
e
in tum
in t
um
ou
r siz
e
–0
–20
–40
–60
–80
–100Phase 1
A Patient previously confirmed partial response
now in unconfirmed CR on treatment
A
83
MA11.07: Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors – Cho BC, et al
• Key results (cont.)
• Conclusions
– In patients with ROS1+ advanced NSCLC, repotrectinib demonstrated promising activity in the TKI-naïve
cohort and was generally well-tolerated
Cho BC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.07
ORR, n/N (%) [95%CI]
Cohort 1 6/7 (86) [42, 100]
Cohort 2 2/5 (40) [5, 85]
Cohort 3 2/5 (40) [5, 85]
Cohort 4 4/6 (67) [22, 96]
Cohort 5 NR
Cohort 6 3/6 (50) [12, 88]
Grade 3 TRAEs, n (%) All treated patients (n=185)
Anaemia 6 (3.2)
Dizziness 4 (2.2)
Dyspnoea 1 (0.5)
Muscular weakness 1 (0.5)
Other malignancies
SCLC, mesothelioma and thymic epithelial tumors
85
PS01.11: Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial – Fennell D, et al
• Study objective
– To assess the efficacy and safety of nivolumab in patients with relapsed malignant mesothelioma
Fennell D, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.11
R
2:1
PD/toxicity/
withdrawal
PD/toxicity/
withdrawal
Stratification
• Histology (epithelioid vs. non-epithelioid)
Key patient inclusion criteria
• Mesothelioma
• >1 prior line of therapy
• ECOG PS 0–1
(n=332)Placebo
(n=111)
Nivolumab 240 mg IV D1 q2w
(n=221)
Co-primary endpoints
• OS, PFS (investigator assessed)
Secondary endpoint
• Response, QoL, safety
86
PS01.11: Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial – Fennell D, et al
• Key results
Fennell D, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.11
Overall survival
Pro
port
ion a
live, %
1.00
0.75
0.50
0.25
0
Time to death, months
302724211815129630
19101924405895132191221
22235918295390111
No. at risk
Nivolumab
Placebo
Nivolumab
(n=221)
Placebo
(n=111)
mOS, mo (95%CI) 9.2 (7.5, 10.8) 6.6 (5.0, 7.5)
12-mo OS, % (95%CI) 39.5 (32.5, 46.3) 26.9 (18.2, 36.4)
HR (95%CI); p-value 0.72 (0.55, 0.94); 0.018
Median follow-up: Nivolumab: 17.1 months; placebo: 14.2 months
Number of events: Nivolumab: n=151; placebo: n=81Nivolumab
Placebo
87
PS01.11: Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial – Fennell D, et al
• Key results (cont.)
Fennell D, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.11
Progression-free survival
Pro
po
rtio
n a
live
with
no
pro
gre
ssio
n,
%
1.00
0.75
0.50
0.25
0
Time to death, months
302724211815129630
0134513264266108221
000002482136111
No. at risk
Nivolumab
Placebo
Nivolumab
Placebo
Nivolumab
(n=221)
Placebo
(n=111)
mPFS, mo (95%CI) 3.0 (7.5, 10.8) 1.8 (5.0, 7.5)
12-mo PFS, % (95%CI) 14.5 (10.2, 19.7) 4.9 (1.8, 10.6)
HR (95%CI); p-value 0.61 (0.48, 0.77); <0.001
88
PS01.11: Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial – Fennell D, et al
• Key results (cont.)
Fennell D, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.11
Nivolumab Placebo
PD-L1 positive n 56 24
mOS, mo (95%CI) 8.0 (7.1, 12.2) 8.7 (5.1, 15.1)
12-mo OS, % (95%CI) 38.6 (25.1, 51.8) 43.6 (21.6, 63.8)
HR (95%CI); p-value 0.95 (0.51, 1.76); 0.864
PD-L1 negative n 94 60
mOS, mo (95%CI) 9.0 (6.6, 11.1) 6.4 (4.5, 8.5)
12-mo OS, % (95%CI) 36.6 (26.4, 46.7) 26.0 (15.1, 38.3)
HR (95%CI); p-value 0.74 (0.51, 1.08); 0.115
Epithelioid n 195 98
mOS, mo (95%CI) 9.4 (7.7, 10.9) 6.6 (5.0, 8.0)
12-mo OS, % (95%CI) 40.0 (32.6, 47.3) 26.7 (17.5, 36.8)
HR (95%CI); p-value 0.71 (0.53, 0.95); 0.021
Non-epithelioid n 26 13
mOS, mo (95%CI) 5.9 (3.6, 18.4) 6.7 (1.8, NA)
12-mo OS, % (95%CI) 34.6 (15.8, 54.3) 30.8 (9.5, 55.4)
HR (95%CI); p-value 0.79 (0.35, 1.79); 0.572
89
PS01.11: Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial – Fennell D, et al
• Key results (cont.)
• Conclusions
– In patients with relapsed malignant mesothelioma, nivolumab demonstrated significant improvements in
survival compared with placebo and was generally well-tolerated
Fennell D, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.11
AEs, n (%)
Nivolumab (n=221) Placebo (n=111)
Any grade Grade ≥3 Any grade Grade ≥3
Any 207 (94) 99 (45) 104 (94) 47 (42)
Serious 90 (41) 80 (36) 49 (44) 43 (39)
90
OA09.06: Nivolumab in Recurrent Malignant Pleural Mesothelioma: Real-World Data From Expanded Access Program In The Netherlands – Belderbos RA, et al
• Study objective
– To assess the efficacy and safety of nivolumab in patients with recurrent malignant pleural mesothelioma in a
real-world setting
*As part of an Expanded Access Program since 2017 Belderbos RA, et al. J Thorac Oncol 2021;16(suppl):Abstr OA09.06
Endpoints
• PFS, OS, safety
Nivolumab 3 mg/kg*
Key patient inclusion criteria
• Malignant pleural mesothelioma
• Any PD-L1 expression
• Disease progression after ≥1
line of chemotherapy
• ECOG PS 0–1
(n=107)
91
OA09.06: Nivolumab in Recurrent Malignant Pleural Mesothelioma: Real-World Data From Expanded Access Program In The Netherlands – Belderbos RA, et al
• Key results
Belderbos RA, et al. J Thorac Oncol 2021;16(suppl):Abstr OA09.06
Overall survivalProgression-free survival
1815129630
PF
S p
rob
ab
ility
1.00
0.75
0.50
0.25
0
No. at risk 2411225078107
Months
Median PFS: 2.3 months
6-month PFS: 23%
1815129630
OS
pro
ba
bili
ty
1.00
0.75
0.50
0.25
0
No. at risk 2411225078107
Months
Median OS: 6.7 months
6-month OS: 60%
12-month OS: 31%
92
OA09.06: Nivolumab in Recurrent Malignant Pleural Mesothelioma: Real-World Data From Expanded Access Program In The Netherlands – Belderbos RA, et al
• Key results (cont.)
• Conclusions
– In patients with recurrent malignant pleural mesothelioma in a real-world setting, nivolumab did not provide
the same benefits as observed in clinical trials with worse ORR and mOS, particularly in those with no PD-L1
expression or low albumin levels
Belderbos RA, et al. J Thorac Oncol 2021;16(suppl):Abstr OA09.06
Nivolumab
mOS, mo Epithelioid (n=78) 7.4
Non-epithelioid (n=22) 4.8
PR (n=11) NR
SD (n=28) 10.2
PD (n=39) 6.4
Albumin <38 mg/dL (n=22) 2.5
Albumin >38 mg/dL (n=21) 8.0
Nivolumab
mPFS, mo PD-L1 positive (n=11) 4.2
PD-L1 negative (n=22) 1.7
ORR,% PD-L1 positive (n=11) 36
PD-L1 negative (n=22) 9
OR (95%CI); p-value 1.31 (1.00,1.72); 0.05
93
OA11.03: A Phase 1 Study of AMG 757, Half-Life Extended Bispecific T-Cell Engager (BiTE®)Immune Therapy Against DLL3, in SCLC – Owonikoko TK, et al
• Study objective
– To assess the efficacy and safety of AMG 757, a bispecific T-cell engager immune therapy against DLL3, in
patients with SCLC
Owonikoko TK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.03
Endpoints
• Antitumor activity, PK, safety
AMG 757 0.003–30.0 mg IV
q2w with/out step dose
Key patient inclusion criteria
• SCLC
• ≥1 line systemic therapy
• Disease progression or recurrence after
≥1 platinum-based chemotherapy
• ECOG PS 0–2
(n=40)
94
OA11.03: A Phase 1 Study of AMG 757, Half-Life Extended Bispecific T-Cell Engager (BiTE®)Immune Therapy Against DLL3, in SCLC – Owonikoko TK, et al
• Key results
*Step dosing; †PR is unconfirmed; ‡patient had an initial PR but was not confirmed at next scan Owonikoko TK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.03
Modified RECIST v1.1
response, n (%) n=51
PR confirmed 7 (14)
0.3 mg target dose 1/12 (8)
1 mg target dose 1/8 (13)
3 mg target dose 3/9 (33)
10 mg target dose 2/10 (20)
PR unconfirmed 1 (2)
30 mg target dose 1 (2)
SD 11 (22)
DCR, % 37
100
80
60
40
20
0
–20
–40
–60
–80
–100
Be
st %
ch
an
ge
fro
m b
ase
line
in s
um
of d
iam
ete
rs
PD
PD
PDPD PD PD PD PD
PD PD PD PD PD PD PD PD PD NE SD
SDSD PD SD SD
SD
SDSD
SD
SD‡
PD PD
PDPR
PR PRPR
PRPR
PR†PR
0.003mg 0.01mg 0.03mg 0.1mg 0.3mg
1mg 3mg* 10mg* 30mg*
Patients with target lesion and evaluable post-baseline assessment, including sum of diameters (n=42)
PD
SD
95
OA11.03: A Phase 1 Study of AMG 757, Half-Life Extended Bispecific T-Cell Engager (BiTE®)Immune Therapy Against DLL3, in SCLC – Owonikoko TK, et al
• Key results (cont.)
• Conclusions
– In patients with SCLC, AMG 757 demonstrated activity and had an manageable safety profile
*One patient with grade 5 pneumonitis Owonikoko TK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.03
TRAEs occurring in ≥10% of patients, n (%) All grades Grade ≥3
Any 41 (79) 12 (23)
CRS 23 (44) 1 (2)*
Pyrexia 10 (19) 0 (0)
Fatigue 7 (14) 0 (0)
Anaemia 5 (10) 1 (2)
Nausea 5 (10) 0 (0)
96
OA11.06: IMpower133: Exploratory Analysis of Maintenance Therapy in Patients With Extensive-Stage Small-Cell Lung Cancer – Reck M, et al
• Study objective
– To assess the efficacy and safety of atezolizumab vs. placebo in patients with extensive-stage SCLC who
had reached maintenance therapy phase of the IMpower133 study
*Carboplatin AUC 5 mg/mL/min IV q3w; etoposide 100 mg/m2 IV D1–3 q3w for four 21-day cycles Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.06
R
1:1
PD/loss of
benefit
PD/loss of
benefit
Stratification
• Sex (male vs. female)
• ECOG PS (0 vs. 1)
• Brain metastases (yes vs. no)
Key patient inclusion criteria
• Measureable extensive-stage
SCLC
• No prior systemic therapy
• Treated asymptomatic brain
metastases were eligible
• ECOG PS 0–1
(n=403)
Placebo +
carboplatin + etoposide*
(n=202)
Atezolizumab 1200 mg IV D1 q3w
+ carboplatin + etoposide*
(n=201)
Placebo
Atezolizumab
Primary endpoints
• OS, PFS (RECIST v1.1)
Secondary endpoint
• Safety
Induction Maintenance
97
OA11.06: IMpower133: Exploratory Analysis of Maintenance Therapy in Patients With Extensive-Stage Small-Cell Lung Cancer – Reck M, et al
• Key results
Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.06
Atezolizumab
+ CP/ET (n=154)
Placebo
+ CP/ET (n=164)
OS from start of maintenance, HR (95%CI) 0.59 (0.43, 0.81)
mOS from start of maintenance, months (95%CI) 12.5 (9.0, 14.5) 8.4 (7.0, 9.4)
mOS from randomisation, months (95%CI) 15.7 (12.3, 17.6) 11.3 (10.1, 12.2)
Atezolizumab
+ CP/ET (n=154)
Placebo
+ CP/ET (n=164)
PFS from start of maintenance, HR (95%CI) 0.64 (0.50, 0.82)
mPFS from start of maintenance, months (95%CI) 2.6 (2.3, 2.9) 1.8 (1.4, 2.3)
mPFS from randomisation, months (95%CI) 5.5 (4.9, 5.6) 4.5 (4.3, 5.4)
Overall survival Progression-free survival
OS
, %
100
80
60
40
20
0
Time, months
181614121086420 242220
51120324355708497110118127138150154154154154154 123
No. at risk
Atezo
+CP/ET
Placebo
+CP/ET3813202532557589103118131145154163164164164164 223
Atezolizumab + CP/ET
Placebo + CP/ET
PF
S, %
100
80
60
40
20
0
Time, months
181614121086420 242220
2331111142025283140455387134143152154154 112
No. at risk
Atezo
+CP/ET
Placebo
+CP/ET33568813142022274176142157163164164
Atezolizumab + CP/ET
Placebo + CP/ET
98
OA11.06: IMpower133: Exploratory Analysis of Maintenance Therapy in Patients With Extensive-Stage Small-Cell Lung Cancer – Reck M, et al
• Key results (cont.)
• Conclusions
– In patients with extensive-stage SCLC, maintenance atezolizumab + carboplatin/etoposide contributed to
survival benefit over carboplatin/etoposide alone and safety was comparable between the two treatment arms
– Higher age, higher LDH level and reduced performance status were poor prognostic factors to reach the
maintenance therapy phase in both arms (data not shown)Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.06
AEs, n (%)
From randomisation (induction + maintenance) From start of maintenance
Atezolizumab (n=155) Placebo (n=163) Atezolizumab (n=155) Placebo (n=163)
Any 155 (100) 159 (98) 127 (82) 118 (72)
TRAE 151 (97) 153 (94) 76 (49) 61 (37)
Atezolizumab/placebo 100 (65) 86 (53) 64 (41) 41 (25)
Grade 3–4 105 (68) 105 (64) 43 (28) 37 (23)
Treatment-related grade 5 0 (0) 1 (<1) 0 (0) 1 (<1)
Serious 52 (34) 47 (29) 24 (15) 19 (12)
Led to dose modification/interruption 111 (72) 100 (61) 30 (19) 17 (10)
Atezolizumab/placebo 96 (62) 85 (52) 28 (18) 17 (10)
Immune-related 64 (41) 46 (28) 41 (26) 24 (15)
99
MA12.10: Treatment and Survival Differences in Patients with Large Cell Neuroendocrine Carcinoma of the Lung: A SEER Database Analysis – Chen J-H, et al
• Study objective
– To assess the differences in treatment and survival and identify predictors of response in patients with large
cell neuroendocrine carcinoma (LCNEC) of the lung
• Methods
– Data for 2838 patients with LCNEC from the Surveillance, Epidemiology, and End-Results (SEER) database
were collected to evaluate age, sex, race and tumour site, size, grade and stage
– Factors associated with OS and cancer-specific survival (CSS) were assessed using multivariate logistic and
Cox regression
Chen J-H, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.10
100S = surgery, R = radiotherapy, C = chemotherapy
MA12.10: Treatment and Survival Differences in Patients with Large Cell Neuroendocrine Carcinoma of the Lung: A SEER Database Analysis – Chen J-H, et al
• Key results
Chen J-H, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.10
Analysed overall survival and cancer-specific survival in different stages
OS rate, % 1-year 3-year 5-year
S 72.4 52.4 42.3
S + R 62.8 30.1 16.9
S + C 83.3 57.2 48.5
R + C 42.7 12.1 8.0
CSS rate, % 1-year 3-year 5-year
S 83.3 61.6 53.5
S + R 62.8 31.5 17.6
S + C 85.9 62.7 55.2
R + C 45.4 15.3 9.5
OS
, %
100
80
60
40
20
0
150100500
P<0.0001Stage 1
Stage 2
Stage 3
Stage 4
Ove
rall
CS
S, %
100
80
60
40
20
0
150100500
P<0.0001Stage 1
Stage 2
Stage 3
Stage 4
OS
, %
100
80
60
40
20
0
150100500
S
S + R
S + C
R + C
Effects of treatments in patients with L-LCNEC
Ove
rall
CS
S, %
100
80
60
40
20
0
150100500
S
S + R
S + C
R + C
Survival time, months Survival time, months
101
MA12.10: Treatment and Survival Differences in Patients with Large Cell Neuroendocrine Carcinoma of the Lung: A SEER Database Analysis – Chen J-H, et al
• Key results (cont.)
• Conclusions
– In patients with large cell neuroendocrine carcinoma of the lung, surgery and chemotherapy demonstrated
significant improvements in OS and CSS
– Age ≥80 years, stage III and IV or tumour size >5 cm were found to be independent poor prognostic factors Chen J-H, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.10
Characteristic n (%)
Univariate analysis Multivariate analysis
HR (95%CI) p-value HR (95%CI) p-value
Age, years <60
60–79
≥80
796 (28.0)
1774 (62.5)
268 (9.5)
Reference
1.315 (1.111, 1.556)
2.661 (1.919, 3.688)
0.001
<0.0001
Reference
1.352 (1.136, 1.609)
1.841 (1.313, 2.582)
0.001
<0.0001
Sex Male
Female
1591 (56.1)
1247 (43.9)
Reference
0.815 (0.707, 0.940) 0.005
Reference
0.775 (0.664, 0.905) 0.001
Stage I
II
III
IV
664 (23.4)
162 (5.7)
556 (19.6)
1391 (49.0)
Reference
1.896 (1.293, 2.781)
3.795 (2.910, 4.948)
6.763 (5.417, 8.444)
0.001
<0.0001
<0.0001
Reference
1.669 (1.007, 2.765)
2.053 (1.371, 3.074)
3.878 (2.595, 5.796)
0.047
<0.0001
<0.0001
Tumour size ≤3
3–5
>5
Unknown
977 (34.4)
641 (22.6)
735 (26.5)
467 (16.5)
Reference
1.255 (1.031, 1.527)
1.992 (1.651, 2.404)
2.675 (2.162, 3.310)
0.024
<0.0001
<0.0001
Reference
1.182 (0.902, 1.549)
1.391 (1.071, 1.808)
1.362 (1.004, 1.848)
0.226
0.013
0.047
Surgery No
Yes
1861 (65.6)
977 (34.4)
Reference
0.199 (0.166, 0.240) <0.0001
Reference
0.553 (0.397, 0.770) <0.0001
Chemotherapy No
Yes
1338 (47.1)
1500 (52.9)
Reference
0.653 (0.567, 0.752) <0.0001
Reference
0.455 (0.392, 0.528) <0.0001
102
MA12.11: What Regimen Should Be Chosen for Pulmonary Large Cell Neuroendocrine Carcinoma? A Systemic Review and Meta-Analysis – He J, et al
• Study objective
– To assess the outcomes of different regimens for patients with pulmonary large cell neuroendocrine
carcinoma (LCNEC)
• Methods
– A search of electronic databases was conducted to identify studies that provided prognostic outcomes of
SCLC and NSCLC regimen in patients with LCNEC
– In total 6 studies were identified that included 446 patients, 213 with NSCLC and 165 with SCLC received 1L
chemotherapy, while 42 with NSCLC and 26 with SCLC received adjuvant chemotherapy
He J, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.11
103
MA12.11: What Regimen Should Be Chosen for Pulmonary Large Cell Neuroendocrine Carcinoma? A Systemic Review and Meta-Analysis – He J, et al
• Key results
He J, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.11
First-line chemotherapy
Author Year HR (95%CI) % Weight
Rossi
Sun
Naidoo
Derks 1
Derks 2
Eldessouki
Zhang
Overall (I-squared
= 96.7%, p=0.000)
2005
2012
2016
2017
2017
2018
2019
0.05 (0.02, 0.10)
0.27 (0.13, 0.52)
9.69 (4.35, 21.57)
2.68 (1.83, 3.92)
0.59 (0.31, 1.10)
0.89 (0.32, 2.49)
0.12 (0.07, 0.22)
0.73 (0.58, 0.92)
9.17
11.43
8.25
36.13
13.18
4.95
16.87
100.00
0.1 0.5 2 101SCLC regimen NSCLC regimen
Adjuvant chemotherapy
Author Year HR (95%CI) % Weight
Rossi
Zheng
Overall (I-squared
= 80.2%, p=0.025)
2005
2019
0.02 (0.01, 0.04)
0.08 (0.03, 0.23)
0.03 (0.02, 0.07)
55.16
44.84
100.00
0.005 0.05 0.5 5SCLC regimen NSCLC regimen
Overall survival
104
MA12.11: What Regimen Should Be Chosen for Pulmonary Large Cell Neuroendocrine Carcinoma? A Systemic Review and Meta-Analysis – He J, et al
• Key results (cont.)
• Conclusions
– In patients with large cell neuroendocrine carcinoma, 1L SCLC therapies demonstrated improvements in OS
and PFS, while adjuvant SCLC chemotherapy regimens provided improvement in OS
– Conclusions are limited as based on huge heterogeneity of results – further collection of controlled data is of
paramount importance He J, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.11
Progression-free survival for first-line chemotherapy
Year HR (95%CI) % WeightAuthor
Sun
Naidoo
Derks 1
Derks 2
Zhang
Overall (I-squared
= 96.7%, p=0.000)
2012
2016
2017
2017
2019
0.51 (0.28, 1.01)
0.89 (0.40, 1.95)
1.82 (1.22, 2.71)
0.54 (0.28, 1.00)
0.34 (0.23, 0.48)
0.68 (0.54, 0.85)
10.71
7.99
30.83
12.21
38.25
100.00
0.25 0.5 21SCLC regimen NSCLC regimen