TPD DIGEST: September 2021 ESMO Congress Post-

Thursday, September 30, 2021

TPD DIGEST:September 2021ESMO Congress Post-Conference ReportCopyright: Hanson Wade 2021

This Digest has been created through considerable effort by Hanson Wade’s Beacon TPD research team. The terms of subscription restrict usage of this work to those who are named subscribers to the service. Unauthorized copying and/or distribution of this document constitutes copyright infringement. If you are in doubt about whether you are entitled to receive a copy of this Digest, check with your account holder or with Hanson Wade ([email protected])

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Welcome

• Earlier this month the European Society for Medical Oncology (ESMO) held their annual congress.

• In total, 23 abstracts were presented which are associated with a trial on Beacon TPD.

• This month’s digest provides an analysis of these abstracts, looking at the type of data presented.

• The analysis is followed by the summaries of all abstracts, grouped by clinical data and trial outlines, with links to the

relevant Beacon pages.

Table of Contents

• Monthly Updates

• Abstract Analysis

• Trial Data and Outlines

• Summary & Coming Up

Welcome to September


Phase Distribution

Monthly Updates: Trials Added

1

5

1

4

3

2

0

1

2

3

4

5

6

Early Phase I Phase 1 Phase 1/2 Phase 2 Phase 3 Phase Unknown

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Therapeutic Class Distribution


9

4

3

1 1 1

0

1

2

3

4

5

6

7

8

9

10

IMiD SERD Proteasome Inhibitor E3 Modulator Bivalent Degrader Protein Degrader

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Table of Trials Added


Trial ID Phase Sponsor Disease Indication Drug Names

ChiCTR2100050786

Early

Phase 1 The Affiliated Hospital of Xuzhou Medical University

B-Cell Lymphoma, Central Nervous System

Lymphoma Lenalidomide

NCT04951778 1 Celgene

Myelodysplastic Syndrome, Acute Myeloid

Leukemia CC-91633

NCT05050097 1 Janssen Research & Development, LLC Multiple Myeloma

Lenalidomide,

Pomalidomide,

Carfilzomib

HWID39189 1 Accutar Biotechnology Inc Breast Cancer AC0682

2020-003178-34 1 Aileron Therapeutics Healthy Volunteers ALRN-6924

NCT05052970 1 CSPC ZhongQi Pharmaceutical Technology Co. Multiple Myeloma Bortezomib

NCT05054374 1/2 Memorial Sloan-Kettering Cancer Center Breast Cancer, Solid Tumors Fulvestrant

NCT05032820 2 Medical College of Wisconsin Multiple Myeloma Lenalidomide

NCT05050305 2 Dana-Farber Cancer Institute Multiple Myeloma, CNS Tumors

Pomalidomide,

Marizomib

NCT05050630 2 Affiliated Hospital to Academy of Military Medical Sciences

Hodgkin Lymphoma, Non-Hodgkin

lymphoma, High Grade B-cell Lymphoma,

Diffuse Large B-Cell Lymphoma Lenalidomide

ChiCTR2100051262 2 Changzhou Pharmaceutical Factory Advanced Colorectal Cancer Thalidomide

CTR20212307 3 Sihuan Pharmaceutical Holdings Group, XuanZhu Pharma Co Ltd Breast Cancer Fulvestrant

NCT05028348 3 European Myeloma Network Multiple Myeloma Pomalidomide

NCT05038735 3 Novartis Pharmaceuticals Breast Cancer Fulvestrant

NCT05047848 U Liaoning Tumor Hospital & Institute Breast Cancer Fulvestrant

NCT05058755 U

Xinhua Hospital affiliated to Shanghai Jiaotong University, School

of Medicine Extranodal NK/T- cell lymphoma Lenalidomide

https://data.beacon-intelligence.com/drug/187




















Phase Distribution

Monthly Updates: Trials Updates

1

41

25

64

42

31

0

10

20

30

40

50

60

70

Early Phase 1 Phase 1 Phase 1/2 Phase 2 Phase 3 Phase 4 Phase Unknown

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Recruitment Status Distribution


67

62

22

15

4 42 1

0

10

20

30

40

50

60

70

80

Recruitingparticipants

Active notrecruiting

Completed Not yet recruiting Terminated Unknown Suspended Enrolling byinvitation

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Table of Trial Updates


Trial ID Phases Trial Status Sponsor

NCT04065555 Early Phase 1 Recruiting participants Presage Biosciences

NCT01877382 1 Active not recruiting Daiichi Sankyo, Inc.

NCT04895410 1 Recruiting participants Abbvie

NCT03432741 1 Recruiting participants Mayo clinic

NCT02942095 1 Active not recruiting M.D. Anderson Cancer Center

NCT03269136 1 Active not recruiting Pfizer

NCT03449381 1 Recruiting participants Boehringer Ingelheim

NCT04242953 1 Recruiting participants Sun Pharma Advanced Research Company (SPARC)

NCT02734615 1 Active not recruiting Novartis Pharmaceuticals

NCT04956302 1 Not yet recruiting Ohio State University Comprehensive Cancer Center

NCT01965353 1 Completed Dana-Farber Cancer Institute

NCT04247126 1 Recruiting participants Syros Pharmaceuticals

ACTRN12613000283774 1 Terminated Celgene, The Alfred Hospital

NCT02513186 1 Active not recruiting Sanofi

NCT04912427 1 Not yet recruiting Washington University School of Medicine


NCT01661400 1 Recruiting participants Washington University School of Medicine

NCT03767335 1 Recruiting participants Menarini Group

NCT04940026 1 Completed Sanofi

NCT04447027 1 Suspended National Cancer Institute (NCI)

NCT05020639 1 Recruiting participants Chia Tai Tianqing (CTTQ) Pharmaceutical Group Co, Ltd

NCT04970901 1 Not yet recruiting ADC Therapeutics S.A.

NCT03798314 1 Completed Mayo clinic

NCT04847453 1 Not yet recruiting National Cancer Institute (NCI)

https://data.beacon-intelligence.com/trial/7772




























NCT04022876 1 Recruiting participants Aileron Therapeutics

NCT02684032 1 Active not recruiting Celcuity

NCT02431208 1 Completed Hoffmann-La Roche

NCT04635683 1 Recruiting participants Ohio State University Comprehensive Cancer Center

NCT03772925 1 Recruiting participants National Cancer Institute (NCI)

NCT04108195 1 Recruiting participants Janssen Research & Development, LLC

NCT04045795 1 Recruiting participants Sanofi

NCT04483505 1 Recruiting participants Fundacion CRIS de Investigación para Vencer el Cáncer

NCT04840888 1 Recruiting participants Eli Lilly and Company

2020-003178-34 1 Unknown Aileron Therapeutics

NCT04172844 1 Active not recruiting Medical College of Wisconsin

NCT03056599 1 Completed Presage Biosciences

NCT01433965 1 Active not recruiting University of California, Davis

NCT01296555 1 Completed Genentech, Inc.

NCT04772885 1 Recruiting participants Kymera Therapeutics

NCT01723020 1 Completed Kartos Therapeutics, Inc

NCT04514159 1 Recruiting participants Zeno Alpha


NCT03939897 1/2 Suspended National Cancer Institute (NCI)

NCT03643549 1/2 Recruiting participants Haukeland University Hospital

NCT03280563 1/2 Recruiting participants Hoffmann-La Roche

NCT01638936 1/2 Completed Biotest Pharmaceuticals Corporation

NCT03319537 1/2 Recruiting participants Memorial Sloan-Kettering Cancer Center

NCT02119468 1/2 Unknown City of Hope Medical Center





























NCT04072952 1/2 Recruiting participants Arvinas

NCT03481556 1/2 Active not recruiting Oncopeptides

NCT03560531 1/2 Recruiting participants Zeno Alpha

NCT03363893 1/2 Active not recruiting Carrick Therapeutics Limited

NCT04973605 1/2 Recruiting participants BeiGene

NCT02384083 1/2 Completed PETHEMA Foundation

NCT01946152 1/2 Terminated M.D. Anderson Cancer Center

NCT03393013 1/2 Recruiting participants Kezar Life Sciences

NCT05025800 1/2 Not yet recruiting M.D. Anderson Cancer Center

NCT02004275 1/2 Active not recruiting Alliance for Clinical Trials in Oncology

NCT02773030 1/2 Recruiting participants Celgene

NCT04699188 1/2 Recruiting participants Novartis Pharmaceuticals

NCT04539236 1/2 Not yet recruiting University of Miami

NCT03715478 1/2 Recruiting participants Canadian Myeloma Research Group

NCT03284957 1/2 Recruiting participants Sanofi

NCT04079738 1/2 Active not recruiting Big Ten Cancer Research Consortium

NCT04185883 1/2 Recruiting participants Amgen

NCT04485260 1/2 Recruiting participants Kartos Therapeutics, Inc


NCT03224507 2 Active not recruiting University of Alabama at Birmingham

NCT04850599 2 Not yet recruiting OHSU Knight Cancer Institute

NCT02654132 2 Active not recruiting Bristol-Myers Squibb

NCT02530424 2 Completed Fondazione Michelangelo

NCT04899349 2 Not yet recruiting Novartis Pharmaceuticals





























NCT02728102 2 Active not recruiting National Heart, Lung, and Blood Institute (NHLBI)

NCT02874742 2 Active not recruiting Janssen Research & Development, LLC


NCT02610777 2 Completed Millennium Pharmaceuticals, Inc

NCT04835129 2 Not yet recruiting Medical College of Wisconsin

NCT01415882 2 Recruiting participants Mayo clinic

EUCTR2016-002600-90-BE 2 Active not recruiting HOVON Foundation

NCT03082677 2 Completed Memorial Sloan-Kettering Cancer Center

NCT04024436 2 Recruiting participants Taiho Oncology, Inc.

NCT04033926 2 Active not recruiting Kezar Life Sciences

NCT04436744 2 Active not recruiting Hoffmann-La Roche

NCT02399085 2 Active not recruiting MorphoSys

NCT02217163 2 Completed Singapore General Hospital

NCT03004287 2 Active not recruiting University of Arkansas

NCT02646735 2 Unknown Chinese Academy of Medical Sciences

ACTRN12619001117101 2 Recruiting participants National Health and Medical Research Council, Australia

NCT04876248 2 Not yet recruiting Roswell Park Cancer Institute

NCT04240054 2 Not yet recruiting Medical College of Wisconsin

NCT03763162 2 Recruiting participants M.D. Anderson Cancer Center

NCT02206984 2 Recruiting participants University of Pittsburgh

JPRN-UMIN000029294 2 Enrolling by invitation Japan Breast Cancer Research Group (JBCRG)

NCT05012397 2 Not yet recruiting Rain Therapeutics

NCT03942224 2 Recruiting participants Emory University

ACTRN12616001164482 2 Active not recruiting Celgene





























NCT02532257 2 Active not recruiting M.D. Anderson Cancer Center

NCT01356290 2 Recruiting participants Medical University of Vienna

NCT04738292 2 Recruiting participants University of Wisconsin, Madison

JPRN-jRCTs031180097 2 Completed Nagoya City University Hospital

NCT02955394 2 Active not recruiting University of Colorado, Denver

NCT03834623 2 Active not recruiting H. Lee Moffitt Cancer Center and Research Institute

NCT01946477 2 Recruiting participants Celgene

NCT01572480 2 Active not recruiting National Cancer Institute (NCI), National Institutes of Health Clinical Center (CC)

NCT03500445 2 Recruiting participants University of Chicago

NCT02572492 2 Unknown Aalborg University Hospital

NCT03691493 2 Recruiting participants Emory University

NCT02538198 2 Active not recruiting Memorial Sloan-Kettering Cancer Center

NCT04191616 2 Recruiting participants Amgen

NCT02315716 2 Active not recruiting University College, London

NCT03314636 2 Recruiting participants Oslo University Hospital


NCT04579380 2 Recruiting participants Seagen (Seattle Genetics) Inc.

NCT02279394 2 Active not recruiting Dana-Farber Cancer Institute

NCT02253316 2 Active not recruiting Washington University School of Medicine

NCT04382300 2 Recruiting participants Shanghai Chest Hospital

NCT03520985 2 Terminated Swiss Group for Clinical Cancer Research

NCT02169791 2 Completed Northside Hospital, Inc.

NCT03069326 2 Active not recruiting Memorial Sloan-Kettering Cancer Center

NCT03188172 2 Active not recruiting University of Leeds





























NCT02005289 2 Active not recruiting Ohio State University Comprehensive Cancer Center

NCT03161483 2 Completed Celgene

EUCTR2013-005157-75-BE 2 Active not recruiting HOVON Foundation

NCT02951819 2 Completed Janssen Scientific Affairs, LLC

NCT02507336 2 Active not recruiting University of Miami

NCT03386162 2 Active not recruiting UNICANCER

NCT03731832 2 Recruiting participants GWT-TUD GmbH


NCT02516696 3 Active not recruiting Weill Medical College of Cornell University

NCT02545283 3 Terminated Hoffmann-La Roche


NCT02495922 3 Completed University of Heidelberg Medical Center


NCT04862663 3 Recruiting participants AstraZeneca

NCT04824092 3 Recruiting participants MorphoSys

NCT01734928 3 Active not recruiting Celgene



NCT03792620 3 Recruiting participants Grupo de Estudos Multicentricos em Onco-Hematologia

NCT01942135 3 Active not recruiting Pfizer

NCT01602380 3 Active not recruiting AstraZeneca

NCT02541383 3 Active not recruiting Intergroupe Francophone du Myelome

NCT03268954 3 Active not recruiting Millennium Pharmaceuticals, Inc

NCT04975308 3 Not yet recruiting Eli Lilly and Company






























NCT04270409 3 Recruiting participants Sanofi


NCT03180736 3 Active not recruiting European Myeloma Network

NCT03158688 3 Active not recruiting Amgen


NCT04266795 3 Active not recruiting Takeda

NCT01916252 3 Completed PETHEMA Foundation

NCT04975997 3 Not yet recruiting Celgene



NCT02390869 3 Recruiting participants Fondazione Italiana Linfomi ONLUS

NCT01863550 3 Active not recruiting ECOG-ACRIN Cancer Research Group


NCT04961996 3 Recruiting participants Hoffmann-La Roche


NCT01208766 3 Active not recruiting Stichting Hemato-Oncologie voor Volwassenen Nederland


NCT02107703 3 Active not recruiting Eli Lilly and Company

NCT04680052 3 Recruiting participants Incyte Corporation

NCT03643276 3 Recruiting participants University of Schleswig-Holstein

NCT04305496 3 Recruiting participants AstraZeneca

NCT05020236 3 Not yet recruiting Pfizer

NCT03151811 3 Active not recruiting Oncopeptides




























Trial ID Phase Trial Status Sponsor

NCT04217967 4 Recruiting participants Peking Union Medical College Hospital

NCT03173092 4 Recruiting participants Millennium Pharmaceuticals, Inc

NCT03401372 U Completed Peking Union Medical College Hospital





Trial News: Trial Announcements

Trial News: Results Updates

Monthly Updates: News

Trial ID Announcement

NCT03268954 Study did not achieve pre-defined statistical significance for the primary endpoint

of event-free survival

NCT05025800 ALX Oncology announces initiation of trial of evorpacept in combination with

lenalidomide and rituximab

Trial ID Summary

NCT02004275 Shared results in the American Journal of Hematology

NCT04072952 Provided an update in a company presentation



NCT02942095 Shared results in Investigational New Drugs

NCT02899052 Shared results in Blood Advances

NCT01433965 Shared results in Bone Marrow Transplantation








http://https/data.beacon-intelligence.com/trial/23117



Trial News: Results Updated


Trial ID Summary

NCT02217163 Shared results in the Blood Cancer Journal

NCT01734928 Shared results in the European Journal of Haematology

NCT03393013 & NCT04033926 Provided an update in a company presentation

NCT03401372 Shared results in Circulation





NCT01208766 Shared results in the Journal of Clinical Oncology

NCT02541383 Shared results in The Lancet Oncology

NCT01572480 Shared results in JAMA Oncology

NCT04382300 Shared results in BMC Cancer

NCT02572492 Shared results in the European Journal of Haematology
















Drug News: Regulatory Announcements


Drug Regulatory Announcement

AC0682 Accutar Biotechnology announced FDA clearance of IND

application for phase 1 trial of AC0682 in er-positive breast

cancer

APG-115 Granted fast track designation by the FDA for the treatment

of relapsed/refractory unresectable or metastatic melanoma





Drug News: New Drugs


Developer Drug Name Disease Indication Therapeutic Class

University of Michigan ARD-2585 Prostate Cancer PROTAC

Shanghai Meizer

Pharmaceuticals

Shanghai Meizer

Pharmaceuticals PROTACs

B-cell Lymphoma PROTAC

Icahn School of Medicine at

Mount Sinai, University of

North Carolina

MS83 Cancer Indications PROTAC





Here are this month's highlights from literature exploring early research within the TPD field

• AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss

• Discovery of a Novel BCL-X L PROTAC Degrader with Enhanced BCL-2 Inhibition

Early Papers

https://pubmed.ncbi.nlm.nih.gov/34560429/

https://pubmed.ncbi.nlm.nih.gov/34533954/


Abstract Analysis


Drugs for Clinical Abstracts at ESMO 2021

• Fulvestrant had the highest number of abstracts presented at ESMO 2021, due to the large number of trials currently

investigating the drug.

Abstract Analysis –Trials Presented at ESMO 2021

14

2 2 21 1 1

0

2

4

6

8

10

12

14

16

Fulvestrant ALRN-6924 Amcenestrant ZN-c5 Giredestrant BI 907828 Bortezomib

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Trial Phase Distribution at ESMO 2021

• There is an even distribution of trial phases presented at ESMO 2021, with phase 1 trials being the most common. Half

of the phase 1 trial abstracts were on E3 modulators such as ALRN-6924 and BI 907828.


6

4 4

5

0

1

2

3

4

5

6

7

Phase 1 Phase 1/2 Phase 2 Phase 3

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Trial Status Distribution at ESMO 2021

• The majority of trials presented at ESMO 2021 are still recruiting participants, 7/9 abstracts from trials recruiting

participants were on SERDs such as fulvestrant and ZN-c5.


9

8

2

1

0

1

2

3

4

5

6

7

8

9

10

Recruiting participants Active not recruiting Unknown Completed

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Therapeutic Class Distribution at ESMO 2021

• The most common therapeutic class are SERDs due to the high number of abstracts presented for fulvestrant but also

for other SERDs such as amcenestrant, giredestrant and ZN-c5.

0

2

4

6

8

10

12

14

16

18

20

SERDs E3 Modulators Proteasome Inhibitor

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Abstract Summaries


ESMO Congress –Trial Data Trial ID Abstract

ID

Drug Title Results Safety

NCT01942135 1103P Fulvestrant 177Lu-DOTATATE efficacy and safety

in functioning neuroendocrine tumors:

A joint analysis of phase II prospective

clinical trials

Sixty-eight patients were enrolled, the majority (88.1%)

with a SR. One (1.5%) patient showed a CR, 21

(32.3%) had a PR and 40 (61.5%) SD. At a median

follow-up of 28.9 months (range 2.2-63.2) median PFS

was 33.0 months (95%CI: 27.1-48.2). Median OS

(mOS) had not been reached at the time of the analysis;

the 2-year OS was 87.8 months

Grade 1-2

hematological toxicity

was the most frequent

NCT02530424 141P Fulvestrant Gene-expression pathways and

dynamics during neoadjuvant chemo-

free therapy predict pathologic

complete response in ER+/HER2+

breast cancer (BC)

In the biomarker population, pCR rate was 28.6% and

16.0% in Fulv and NoFulv cohorts, respectively. At week

2, most of these pathways were also predictive of pCR,

with the addition of trafficking and processing of

endosomal toll-like receptors (TLR, p=4.0E-06, adj

p=0.006), with a similar effect in Fulv and NoFulv

cohorts (p=0.001 and p=0.0006, respectively)

No new safety signals

observed

NCT03449381 1548P BI 907828 A Phase Ia/Ib, dose-escalation/expansion

study of the MDM2–p53 antagonist BI

907828 in patients (pts) with

advanced/metastatic sarcoma

Mean plasma exposures (Cmax and AUC0-inf)

increased with dose. DCR defined as CR + PR + SD)

was 88.9%. 3 of 7 pts with well-differentiated LPS

achieved a PR (all were MDM2-amplified); 1 remained

on treatment >2 years. All 11 pts with DDLPS achieved

SD as best overall response; the median PFS was

approximately 10.8 months (range, 1.3–21 months)

5 patients

experienced DLTs in

arm A and 3 in arm B.

Most common G 3/4

AEs were TCP

(29.6%) and

neutropenia (22.2%)


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/177lu-dotatate-efficacy-and-safety-in-functioning-neuroendocrine-tumors-a-joint-analysis-of-phase-ii-prospective-clinical-trials



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/gene-expression-pathways-and-dynamics-during-neoadjuvant-chemo-free-therapy-predict-pathologic-complete-response-in-er-her2-breast-cancer-bc



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/a-phase-ia-ib-dose-escalation-expansion-study-of-the-mdm2-p53-antagonist-bi-907828-in-patients-pts-with-advanced-metastatic-sarcoma



Trial ID Abstract

ID


2019-001848-21 1654P ALRN-6924 A Phase 1b/2 Study of the Dual

MDMX/MDM2 Inhibitor, ALRN-6924,

for the Prevention of Chemotherapy-

induced Myelosuppression

Results compare favorably to recent

historical results of 63%, 70% and 76%,

respectively. None of the patients treated

at the 0.3 mg/kg ALRN 6924 dose level

had a related SAE; 6% required RBC

and platelet transfusions

No patients reported NCI CTC Grade

≥3 events of nausea, vomiting,

diarrhea; 5% had Grade 3 fatigue.

0.3 mg/kg ALRN 6924 dose level 24

hr prior to topo showed the most

favorable chemoprotection results,

with NCI CTC Grade 3/4 anemia and

thrombocytopenia limited to 19% and

50% of patients, respectively, and a

44% rate of Grade 4 neutropenia

2020-003178-34 1791P ALRN-6924 A Phase 1 Pharmacology Study of the

Dual MDMX/MDM2 Inhibitor, ALRN

6924, in Healthy Volunteers

Robust p21 induction was observed in

bone marrow cells, with peak expression

between 4 hr and 16 hr following ALRN-

6924 administration

Subjects experienced only mild,

transient AEs

NCT02333370 232P Fulvestrant Longitudinal circulating tumor DNA

(ctDNA) analysis in the phase 1b

MONALEESASIA study of ribociclib

(RIB) + endocrine therapy (ET) in

Asian patients (pts) with hormone

receptor–positive (HR+)/human

epidermal growth factor receptor 2–

negative (HER2–) advanced breast

cancer (ABC)

There was a consistent trend of lower BL

ctDNA levels in pts with partial response

(PR) or stable disease (SD) vs pts with

progressive disease; however, there was

no difference in ctDNA levels at on-

treatment time points and EOT by BOR

No new safety signals observed

ESMO Congress –Trial Data


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/a-phase-ib-ii-study-of-the-dual-mdmx-mdm2-inhibitor-alrn-6924-for-the-prevention-of-chemotherapy-induced-myelosuppression



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/a-phase-i-pharmacology-study-of-the-dual-mdmx-mdm2-inhibitor-alrn-6924-in-healthy-volunteers



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/longitudinal-circulating-tumor-dna-ctdna-analysis-in-the-phase-1b-monaleesasia-study-of-ribociclib-rib-endocrine-therapy-et-in-asian-patien




Trial ID Abstract

ID


NCT01942135 234P Fulvestrant Effect of palbociclib (PAL) +

endocrine therapy (ET) on time

to chemotherapy (TTC) across

subgroups of patients (pts) with

hormone receptor-

positive/human epidermal

growth factor receptor 2-

negative (HR+/HER2-)

advanced breast cancer (ABC):

Post hoc analyses from

PALOMA-2 (P2) and PALOMA-

3 (P3)

Higher percentage of pts who received vs

who did not receive first subsequent CT

were aged <65 (80% vs 64% in P3, 77%

vs 71% in P3) or had a disease-free

interval (DFI) of ≤12 months


NCT02646735 235P Fulvestrant Efficacy and safety of first-line

therapy with fulvestrant or

exemestane for

postmenopausal ER+/HER2-

advanced breast cancer

patients after adjuvant

nonsteroidal aromatase

inhibitor treatment: A

randomized, open-label,

multicenter study

Median PFS 8.51 months in fulvestrant

group versus 5.55 months in exemestane

group (P = 0.014, HR=0.615, 95%Cl:

0.417∼0.907); ORR of the fulvestrant

group was 19.48% compared to 5.97% of

the exemestane group (P =0.017); TTF

was significantly longer for fulvestrant

versus exemestane (median TTF was

8.38 months in the fulvestrant group and

5.45 months in the exemestane group,

P=0.008)

No significant differences in the

incidence of adverse events and

severe adverse events were observed

between the two groups


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/effect-of-palbociclib-pal-endocrine-therapy-et-on-time-to-chemotherapy-ttc-across-subgroups-of-patients-pts-with-hormone-receptor-positiv



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/efficacy-and-safety-of-first-line-therapy-with-fulvestrant-or-exemestane-for-postmenopausal-er-her2-advanced-breast-cancer-patients-after-adjuvan




Trial ID Abstract

ID


NCT02107703 241P Fulvestrant Abemaciclib plus fulvestrant in

participants with HR+/HER2-

advanced breast cancer - a pooled

analysis of the endocrine therapy

naïve (EN) participants in MONARCH

2

Confirmed ORR was 59.1% (95% CI

49.9-68.3). Median follow-up was 9.8

(0.03-73.05) months. PFS and DoR

data are not mature currently

No new safety signals were reported

in the pooled EN cohort, and the

safety profile was consistent with the

previously reported MONARCH 2

population

TBC 253P Fulvestrant Risk factor (RF) identification (ID)

and hyperglycemia (HG) prevention

with alpelisib (ALP) + fulvestrant

(FLV) in PIK3CA-mutated,

hormone-receptor positive (HR+),

human epidermal growth factor-2

negative (HER2-) advanced breast

cancer (ABC)

Median duration of ALP was 86 days

(range 24-442), with 3 pts continuing

to receive ALP at time of analysis

13 pts permanently discontinued ALP

– 9 due to disease progression and 4

due to an adverse event with only 1

due to HG. 9 pts (56%) had G2-4

HG, with only 3 (19%) having G3 HG

and zero having grade 4. Pts with

G2-4 HG had a median of 2 RFs

compared to only 1 RF if no HG

(p=0.03)

NCT03284957 264P Amcenestrant AMEERA-1: Subgroup analyses of

Phase 1/2 study of amcenestrant

(SAR439859), an oral selective

estrogen receptor (ER) degrader

(SERD), with palbociclib in

postmenopausal women with ER+/

human epidermal growth factor

receptor 2-negative (HER2–)

advanced breast cancer (aBC)

In 33 response-evaluable pts with

baseline NGS data: 23 pts had

wtESR1 + other genomic aberrations,

with OR in 6/23 (26.1%) and CB in

16/23 (69.6%); of 11/33 pts with OR,

2/5 had OR and 4/5 had CB; of 9/33

pts with no CB, genomic aberrations

included PIK3CA and TP53



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/abemaciclib-plus-fulvestrant-in-participants-with-hr-her2-advanced-breast-cancer-a-pooled-analysis-of-the-endocrine-therapy-naive-en-participa


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/risk-factor-rf-identification-id-and-hyperglycemia-hg-prevention-with-alpelisib-alp-fulvestrant-flv-in-pik3ca-mutated-hormone-receptor



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/ameera-1-subgroup-analyses-of-phase-i-ii-study-of-amcenestrant-sar439859-an-oral-selective-estrogen-receptor-er-degrader-serd-with-palboci




Trial ID Abstract

ID


2017-002026-20 265P Fulvestrant Study of samuraciclib (CT7001), a

first-in-class, oral, selective inhibitor

of CDK7, in combination with

fulvestrant in patients with

advanced Hormone Receptor

positive HER2 negative breast

cancer (HR+BC)

Evaluation indicates evidence of

reduction in tumor disease

burden, including a partial

response in one patient who has

been on treatment for ∼ 1 year

Combination treatment was generally well

tolerated, with adverse drug reactions

(AE) of note being G1-2 nausea, vomiting

and diarrhoea

NCT03767335 266P Fulvestrant MEN1611, a PI3K Inhibitor,

combined with trastuzumab (T) ±

fulvestrant (F) for HER2+/PIK3CA

mutant (mut) advanced or

metastatic (a/m) breast cancer

(BC): safety and efficacy results

from the ongoing Phase 1b study

(B-PRECISE-01)

In the evaluable population (n=29)

9 pts showed partial response

(MEN+T 4/11, MEN+T+F 5/18),

and 18 pts had stable disease

(MEN+T 6/11, MEN+T+F 10/18)

as best response. 7 pts were on

treatment > 6 months (MEN+T 3,

MEN+T+F 4), and 1 pt received

MEN+T > 12 months

TEAEs, ≥20% were diarrhoea 64.3%,

nausea 42.8%, asthenia 31%, decreased

appetite 28.6%, anaemia 28.6%, and

hyperglycaemia 23.8%. Most TRAEs

were reversible and manageable by

supportive care. TRAEs caused treatment

interruption in 14 pts (33.3%, 1 pt

definitely) and dose reduction in 6 pts

(16.7%, only allowed in CE) mostly

hyperglycaemia, diarrhoea, nausea,

asthenia and decreased appetite. Serious

TRAEs were experienced by 8 pts;

hyperglycaemia 3 pts, diarrhoea 2 pts,

general physical health deterioration,

generalized oedema, and pneumonitis (1

pt each)


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/study-of-samuraciclib-ct7001-a-first-in-class-oral-selective-inhibitor-of-cdk7-in-combination-with-fulvestrant-in-patients-with-advanced-horm



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/men1611-a-pi3k-inhibitor-combined-with-trastuzumab-t-fulvestrant-f-for-her2-pik3ca-mutant-mut-advanced-or-metastatic-a-m-breast-cancer



Trial ID Abstract

ID


NCT03280563 267P Fulvestrant Phase Ib/II open-label, randomized

evaluation of second- or third-line

(2L/3L) atezolizumab (atezo) +

entinostat (entino) in MORPHEUS-

HR+ breast cancer (M-HR+BC)

Confirmed ORRs were 6.7% (95% CI: 0.17,

31.95) and 0% (95% CI: 0, 23.16), respectively.

Duration of response was 2.5 months for

atezo+entino (N/A for control). Median PFS was

1.8 months (95% CI: 1.5, 3.6) and 1.8 months

(95% CI: 1.5, 2.7), respectively

40.0% and 21.4% of pts had

Gr 3/4 AEs; no Gr 5 AEs

occurred; serious AEs (SAEs)

occurred in 26.7% and 14.3%

of pts; 6.7% and 0% of pts

had tx-related AEs leading to

tx withdrawal. The most

common tx-related AEs were

nausea (33.3%), vomiting

(26.7%), fatigue (26.7%),

pyrexia (26.7%) and chills

(20.0%) with atezo+entino

NCT03439046 292P Fulvestrant Serum thymidine kinase 1 activity

in patients with hormone receptor

positive (HR+)/HER2 negative

(HER2-) advanced breast cancer

(aBC) treated in first-line with

ribociclib (R) and letrozole (L) in the

BioItaLEE trial

TKa dynamics were strongly predictive of PFS:

P2 indicated a worse outcome vs P1 (HR 2.89;

95% CI 1.57,5.31; p=0.0006), while P3 was

associated with shortest PFS (HR 5.65; CI

2.84,11.2; p<0.0001). For pts in P2, low TKa


observed



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/phase-ib-ii-open-label-randomized-evaluation-of-second-or-third-line-2l-3l-atezolizumab-atezo-entinostat-entino-in-morpheus-hr-breast-ca



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/serum-thymidine-kinase-1-activity-in-patients-with-hormone-receptor-positive-hr-her2-negative-her2-advanced-breast-cancer-abc-treated-in-fi



Trial ID Abstract

ID


NCT02437318 309P Fulvestrant Antineoplastic (ANP) Therapies (Tx)

After Alpelisib (ALP) or Placebo

(PBO) + Fulvestrant (FUL) in Patients

(Pts) With Hormone Receptor-Positive

(HR+), Human Epidermal Growth

Factor Receptor 2-Negative (HER2–),

PIK3CA-Mutated (Mut) Advanced

Breast Cancer (ABC): An Analysis

From SOLAR-1

In the ALP arm, CT-based 1st subsequent tx was

more frequent in pts with PFS ≤6 mo (56%,

30/54) than pts with PFS >6 mo (40%, 25/63).

FUL and aromatase inhibitors (excluding FUL-

containing regimens) were part of 1st

subsequent tx in 21% (n=24) and 33% (n=39) of

pts in the ALP arm, and 10% (n=14) and 38%

(n=51) of pts in the PBO arm, respectively


observed

TBC 846P Bortezomib Predictive and prognostic values of

serum VEGF in patients with

multiple myelomas receiving

bortezomib-based therapy

Mean ± SEM of VEGF (pg/ml) was 112.09

±13.25, with range of 4.08-419.50. Seventeen

patients (43.6%) had increased level of serum

VEGF. Patients with increased VEGF level had a

≥ VGPR (very good partial response) lesser than

those patients with normal VEGF level (P= .047)


observed

NCT04436744 LBA14 Giredestrant Neoadjuvant giredestrant (GDC-

9545) + palbociclib (palbo) vs

anastrozole (A) + palbo in post-

menopausal women with oestrogen

receptor-positive, HER2-negative,

untreated early breast cancer

(ER+/HER2– eBC): Interim analysis

of the randomised, open-label,

phase 2 coopERA BC study

Ki67 suppression was observed in pts with

baseline Ki67 ≥20% (giredestrant: 83%

reduction; A: 71%) or <20% (65% vs 24%). At

week 2, 25% of tumors exhibited CCCA with

giredestrant vs 5% with A (Δ 20%; 95% CI = –

37%, –3%)

Fewer pts had giredestrant-

vs A-related adverse events

(AEs) (28% vs 38%); no

grade ≥3 AEs or serious AEs

were giredestrant-related



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/antineoplastic-anp-therapies-tx-after-alpelisib-alp-or-placebo-pbo-fulvestrant-ful-in-patients-pts-with-hormone-receptor-positive-hr


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/predictive-and-prognostic-values-of-serum-vegf-in-patients-with-multiple-myelomas-receiving-bortezomib-based-therapy



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/neoadjuvant-giredestrant-gdc-9545-palbociclib-palbo-vs-anastrozole-a-palbo-in-post-menopausal-women-with-oestrogen-receptor-positive-her



ESMO Congress –Trial Outlines

Trial ID Abstract

ID

Drug Title Summary

NCT03284957 333TiP Amcenestrant AMEERA-1: Phase 1/2 study of

amcenestrant (SAR439859), an oral

selective estrogen receptor (ER) degrader

(SERD), with alpelisib in postmenopausal

women with ER+/ human epidermal growth

factor receptor 2-negative (HER2–)

PIK3CA-mutated advanced breast cancer

Primary objective in Part F is to confirm the recommended phase 2 dose

(RP2D) of amcenestrant in combination with alpelisib, based on safety. In

Part G, approximately 34 pts will be treated at the RP2D, the primary

endpoint being safety and tolerability. Secondary endpoints include PK

and antitumor activity. This study is currently recruiting participants

NCT04862663 338TiP Fulvestrant CAPItello-292: a phase 1b/3 study of

capivasertib, palbociclib and fulvestrant

versus placebo, palbociclib and

fulvestrant in HR+/HER2− advanced

breast cancer

CAPItello-292 is a phase 1b/3 study to evaluate the safety and efficacy

of capivasertib, palbociclib and fulvestrant compared with placebo,

palbociclib and fulvestrant in patients with ET-resistant, HR+/HER2– ABC

NCT04579380 557TiP Fulvestrant SGNTUC-019: Phase 2 basket study of

tucatinib and trastuzumab in previously

treated solid tumors with HER2

alterations (Trial in Progress)

SGNTUC-019 is a multi-cohort, open-label, phase 2 study. Cohorts will

enroll pts with HER2+ cervical, uterine, biliary tract, and urothelial

cancers, non-squamous NSCLC, other HER2+ solid tumors (except

GEC, BC, and CRC), HER2-mut non-squamous NSCLC, BC, and other

solid tumors. Primary objective is antitumor activity. Confirmed ORR per

investigator is primary endpoint; secondary endpoints are disease control

rate, DOR, PFS, and OS.


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/ameera-1-phase-i-ii-study-of-amcenestrant-sar439859-an-oral-selective-estrogen-receptor-er-degrader-serd-with-alpelisib-in-postmenopausal



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/capitello-292-a-phase-1b-3-study-of-capivasertib-palbociclib-and-fulvestrant-versus-placebo-palbociclib-and-fulvestrant-in-hr-her2-advanced-br



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/sgntuc-019-phase-ii-basket-study-of-tucatinib-and-trastuzumab-in-previously-treated-solid-tumors-with-her2-alterations



ESMO Congress –Trial Outlines

Trial ID Abstract

ID

Drug Title Summary

NCT04514159 564TiP ZN-c5 A Phase 1b dose-escalation study of ZN-c5,

an oral selective estrogen receptor degrader

(SERD), in combination with abemaciclib in

patients with advanced estrogen receptor

(ER)+/HER2- breast cancer

This phase 1b, open-label, multicenter study is evaluating the safety,

pharmacokinetics, and preliminary anti-tumor activity of ZN-c5 in combination

with abemaciclib. The primary objective is to determine the maximum tolerated

dose and recommended phase 2 dose

NCT03560531 565TiP ZN-c5 A Phase 1/2 dose-escalation and

expansion study of ZN-c5, an oral

selective estrogen receptor degrader

(SERD), as monotherapy and in

combination with palbociclib in patients

with advanced estrogen receptor

(ER)+/HER2- breast cancer

This phase 1/2, open-label, multicenter study is evaluating the safety,

pharmacokinetics, and anti-tumor activity of ZN-c5 alone and in combination

with palbociclib


https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/a-phase-ib-dose-escalation-study-of-zn-c5-an-oral-selective-estrogen-receptor-degrader-serd-in-combination-with-abemaciclib-in-patients-with-ad



https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/a-phase-i-ii-dose-escalation-and-expansion-study-of-zn-c5-an-oral-selective-estrogen-receptor-degrader-serd-as-monotherapy-and-in-combination-w



Summary & Coming Up


Summary

• ESMO 2021 abstracts were mainly centred around SERDs, particularly fulvestrant. This is a reflection of the high clinical

activity in this therapeutic class which does not seem to be slowing down due to the trials still recruiting participants.

• Other therapeutic classes such as E3 modulators and proteasome inhibitors were also present, with assets such as

ALRN-6924 and bortezomib.

• These assets have a large clinical activity so we can expect more data to come in future conferences.

Coming Up

• We hope you found this analysis of ESMO 2021 abstracts useful.

• In the meantime, stay up to date with the latest updates by signing up to our weekly newsletters here

Summary & Coming Up




https://beacon-intelligence.com/solutions/tpd/#TPD-newsletter

Thursday, September 30, 2021

THANK YOU

Sofia Rodriguez

TPD Analyst

[email protected]

MAKING DRUG DEVELOPMENT DECISIONS, FASTER.

Documents

TPD DIGEST: September 2021 ESMO Congress Post-