Manola J et al. Clin Cancer Res 2011;17:5443-5450 International
prognostic model SE Square root of days from diagnosis to study
entry 0.01920.002 ECOG performance status 01.5240.11 ECOG
performance status 10.8380.11 Number of metastatic sites0.3240.032
Protocol immunotherapy0.5740.094 Natural log of hemoglobin2.470.20
Natural log of LDH0.6110.062 Square root of white blood count
0.6230.071 1/Square root of alkaline phosphatase 6.6651.39 Serum
calcium0.1050.033
Slide 4
Treatment: HD IL2 Cytokine Working Group trial HD IL2 vs sc
IL2/IFNA HD IL2: 600,000 IU/kg q8 o x 14 doses sc IL2/IFNA: 5 x 10
6 IU/m 2 4d/wk IL2; 5 x10 6 IU/m 2 2d/wk Selection criteria
Non-clear cell have minimal to no benefit Suggestion that
post-VEGFR TKI treatment has higher toxicity and lower efficacy sc
IL2/IFNAHD IL2 Pt number9195 Deaths11 CR38 (p= 0.21) PR614 Resp.
Duration15 mo24 mo (p=0.18) Med. Surv.13 mo17 mo (p = 0.21) Durable
3 yr CR07 (p=0.01)
Slide 5
Nivolumab (anti-PD1) in renal cancer Population Dose (mg/kg)
Patients (n) ORR n (%) Duration of Response (mo) SD 24 wk n (%)
PFSR at 24 wk (%) ALL RCC1, 10339 (27)5.6+ to 22.3+9 (27)56 RCC
1174 (24) 5.6+ to17.5+ 4 (24)47 10165 (31)* 8.4 to 22.3+ 5 (31)67
*One CR. Phase 3 vs everolimus in progress Multiple PD1 pathway
inhibitor trials in progress
Slide 6
6 MPDL3280A Phase 1a (anti-PDL1) RECIST 1.1 Response Rate (ORR)
SD of 24 Weeks or Longer 24-Week PFS Overall population (N = 140)
21%16%45% RCC* (n = 47) 13%32%53% Clear cell (n = 40) 13% 35%57%
Non-clear cell (n = 6) 17% 020% * 1 patient with unknown histology.
Includes sarcomatoid and papillary RCC. All patients first dosed
prior to August 1, 2012; data cutoff February 1, 2013. ORR includes
unconfirmed PR/CR and confirmed PR/CR. Cho, et al, ASCO 2013
Slide 7
7Renal Cancer| Peptide vaccine IMA901 multi-peptide 10
different tumor-associated Not normal tissue In-vitro immunogenic
HLA-A*02 restricted Pharmaceutical grade Metastatic disease
HLA-A*02 positive No prior therapy N = 330 Sunitinib IMA901 +
GM-CSF 1 st cycle with cyclophosphamide Overall Survival
Slide 8
8Renal Cancer| Dendritic Cell Therapy: AGS-003 RNA isolated
from tumor cells Loaded on dendritic cells isolated through
leukapheresis Administered intradermal Metastatic disease No prior
therapy Cytoreductive nephrectomy N = 450 Sunitinib + AGS-003
Overall Survival
Slide 9
9Renal Cancer| RCC Immunotherapy Conclusions Has always been
considered an immunotherapy responsive tumor HD-IL2 leads to rare
sustained complete responses PD1 pathway inhibitors are promising
Other immunotherapies are being investigated
