NIVO improved OS vs placebo in Asian pts with gastric/gastroesophageal junction cancer in the phase 3 ATTRACTION-2 study (Kang YK, et al. ASCO GI 2017 [abstract 2]). In CheckMate 032, NIVO ± ipilimumab (IPI) demonstrated ORRs of 14% (NIVO monotherapy) and 26% (NIVO 1 mg/kg + IPI 3 mg/kg) in CT-Rx EG cancer (NCT01928394; Janjigian YY, et al. ASCO 2017 [abstract 4014]). The Cancer Genome Atlas identified MSI-high (MSI-H) EG tumors as having therapeutic targets that may make them responsive to immune checkpoint inhibitors. This exploratory analysis evaluated ORR and OS by MSI status in pts with EG cancer treated with NIVO monotherapy in CheckMate 032.
Pts with adv CT-Rx EG (including gastric, esophageal, and gastroesophageal junction) cancer were treated with NIVO 3 mg/kg every 2 weeks (n = 59). MSI status was centrally assessed using a PCR-based assay. Best objective response (BOR), ORR, and DCR (BOR of CR, PR, or SD) per investigator (INV) were assessed per RECIST v1.1.
MSI status was determined in 25 pts; 7 (28%) were MSI-H, and 18 (72%) were non–MSI-H. ORR per INV was 29% in MSI-H pts, 11% in non–MSI-H pts, and 9% in pts with unknown MSI (MSI-U). DCR was 71%, 28%, and 26%, respectively. Of the 7 responders, 3 were PD-L1+ (≥1% tumor expression; 1 per MSI category), 3 were PD-L1− (MSI-U, n = 2; non–MSI-H, n = 1), and 1 was not evaluable for PD-L1 assessment (MSI-H). BOR is shown in the Table. Median OS (95% CI) was 14.75 mo (1.51, NA) in MSI-H pts, 6.49 mo (2.96, 12.42) in non–MSI-H pts, and 5.03 mo (2.76, 16.16) in MSI-U pts. Safety for the full EG cohort was previously reported (Janjigian YY, et al. ASCO 2016 [abstract 4010]).
In this subgroup analysis, 7 pts (28%) were MSI-H, representing a biologically unique subset of EG tumors. NIVO monotherapy led to survival benefit and responses in both MSI-H and non–MSI-H pts.Table:
674P ORR and BOR per INV according to MSI status
|MSI-H n = 7||Non–MSI-H n = 18||MSI-U n = 34|
|ORR, n (%) [95% CI]||2 (29) [4, 71]||2 (11) [1, 35]||3 (9) [2, 24]|
|BOR, n (%)|
|PR||1 (14)||2 (11)||3 (9)|
|SD||3 (43)||3 (17)||6 (18)|
|PD||2 (29)||11 (61)||21 (62)|
|Not evaluable||0||2 (11)||4 (12)|
Clinical trial identification
CA209032 Revised Protocol 06, dated 18-Nov-2015
Legal entity responsible for the study
P.A. Ott: Grants, personal fees and non-financial support from BMS during the conduct of the study; grants/personal fees from BMS, Merck and Celldex, Amgen, Alexion, Pfizer, Cytomx, AZ/MedImmune and ArmoBiosciences outside the submitted work. P.A. Ascierto: Grants and personal fees from BMS, Roche-Genentech, MSD, Array, Novartis, Amgen,Merck Serono, and Pierre Fabre outside the submitted work P. Sharma: Consultant/Advisor for BMS, GSK, AstraZeneca, Amgen, Constellation, Jounce, Kite Pharma, Neon, Evelo, EMD Sereno, and Astellas, during the conduct of the study; Stock with Jounce, Kite Pharma, Evelo, Constellation, and Neon. Has a patent Jounce licensed P. Bono: Honoraria from Pfizer, BMS, Orion Pharma, Novartis and MSD, research grant from Novartis, outside the submitted work; Stock Ownership: Tilt Biotherapeutics K. Peltola: Personal fees from BMS, Roche, Orion Pharma, and MSD, outside the submitted work; Stock Holder: Faron Pharmaceuticals D. Jäger: Consulting/advisory role for Roche, BMS and Bayer T.R.J. Evans: Personal fees/non-financial support from BMS, Eisai, Clovis, Karus Therapeutics, Baxalta, Bayer, Celgene, GSK, Otsuka, Roche-Genentech, TC Biopharm, Immunova, Basilea, e-Therapeutics, Immunocore, Vertex, Verastem, Daiichi and Merck F. de Braud: Advisory boards and/or travel support from Amgen, Celgene, Novartis, Roche, BMS, MSD I. Chau: Advisory Board: Sanofi Oncology, Eli-Lilly, Bristol Meyers Squibb, MSD, Bayer, Roche, Five Prime Therapeutics; Research funding: Janssen-Cilag, Sanofi Oncology, Merck-Serono, Novartis; Honorarium: Taiho, Pfizer, Amgen, Eli-Lilly, Gilead Science J.C. Bendell: Payment to institution from the study sponsor for performing the study M. Tschaika, C.T. Harbison: Employee and stock holder at BMS H. Zhao: Employee of BMS E. Calvo: Personal Fees/Non-financial support: Astellas Pharma, GSK, Lilly/ImClone, Nanobiotix, Novartis, Pfizer, Roche/Genentech, PsiOxus Ther, Abbvie, Boehringer Ingelheim, BMS, Eisai, Janssen, Merck, Millenium, Nektar, OncoMed, PharmaMar, Puma Biotech, Sanofi, Spectrum Pharm. All other authors have declared no conflicts of interest.