In the CheckMate 142 trial (NCT02060188), NIVO + IPI demonstrated manageable safety and clinical activity characterized by an investigator-assessed objective response rate (ORR) of 55%, disease control rate (DCR; defined as CR + PR + SD ≥ 12 wk) of 79%, and encouraging survival benefit (6-mo PFS and OS rates:77% and 89%) in pts with dMMR/MSI-H mCRC (Andre T, et al. ASCO 2017). Here, we report biomarker analyses in pts who received NIVO + IPI in the CheckMate 142 study.
Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥ 1 prior line of therapy received NIVO 3 mg/kg + IPI 1 mg/kg Q3W × 4 doses followed by NIVO 3 mg/kg Q2W. Tumor anti-programmed death ligand 1 (PD-L1) expression was assessed using the Dako 28-8 pharmDx assay. PD-L1 positivity was defined as ≥ 1% cell membrane staining of any intensity. BRAF and KRAS mutation statuses were determined by investigators per local guidelines. Characterization of Lynch syndrome as present or absent was based on past medical history from clinical records. ORR per investigator was determined per RECIST v1.1.
Tumor PD-L1 expression and BRAF/KRAS statuses were assessed in 84 pts. ORR and DCR by PD-L1, BRAF/KRAS mutational status, and clinical history of Lynch syndrome are reported in the Table below.
Confirmed responses with NIVO + IPI were observed in pts with dMMR/MSI-H mCRC who were PD-L1 expressors and non-expressors, as well as across BRAF and KRAS mutational status. Responses were also observed in pts with or without a history of Lynch syndrome. These results are consistent with previously reported biomarker analyses of the NIVO monotherapy cohort.Table:
|Pts, n (%) [95%CI]||dMMR/MSI-H mCRC N = 84 Pts With ≥ 6 Mo of Follow-Up|
|Tumor PD-L1 expression*|
|≥1% (n = 16)||9 (56) [29.88, 80.25]||12 (75) [47.62, 92.73]|
Clinical trial identification
Clinical Protocol CA209142. The release date 18-Nov-2013.
Legal entity responsible for the study
T. André: Personal fees: Bristol-Myers Squibb, Roche, Servier, Baxter, Novartis, MSD, Amgen, Lilly, Sanofi, Halliodx, Xbotech and Boehringer Ingelheim. Non-financial support: Roche and BMS. M. Overman: Grantes and personal fees from BMS, outside the submitted work. S. Lonardi: Personal Fees: Amgen; Bayer; Lilly; Roche and Sanofi. M. Aglietta: Advisory board with BMS. R. McDermott: Personal fees: Clovis, Pfizer, and BMS; research funding from Merck, BMS, Janssen, and Bayer; grants from Pfizer, Celgene, and Amgen outside the submitted work. K.Y.M. Wong: Other from BMS, during the conduct of the study. M. Morse: Grants from BMS, during the conduct of the study. R.A. Moss: Employee and stock holder of BMS. J-M. Ledeine: Personal fees from Bristol-Myers Squibb, during the conduct of the study. H. Tang: Employee of BMS. Z.A. Cao: Employee of BMS and a stockholder of BMS and Novartis. S. Kopetz: Consulting/Advisor roles: Amgen, Array BioPharma, Bayer, BMS, Genentech, GSK, Janssen, Merrimack, MolecularMatch, Oculose LLC, Roche, Sanofi, Sirtex Medical, Taiho Pharmaceutical, Rsch Funding-Agendia, Amgen, Biocartis, GSK, Guardant Health, Roche, Sanofi, Sysmex; other: MolecularMatch. All other authors have declared no conflicts of interest.