479P - Nivolumab ± ipilimumab treatment (Tx) efficacy, safety, and biomarkers in patients (Pts) with metastatic colorectal cancer (mCRC) with and without...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Michael Overman
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors M.J. Overman1, S. Kopetz2, S. Lonardi3, R. McDermott4, F. Leone5, J. Leach6, H. Lenz7, A. Hendlisz8, M. Morse9, P. Garcia-Alfonso10, J. Desai11, A. Hill12, R.A. Moss13, M.V. Goldberg13, C. Lin14, H. Tang13, T. André15
  • 1Gastrointestinal Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2Department Of Gastrointestinal (gi) Medical Oncology, Division Of Cancer Medicine, MD Anderson Cancer Center, Houston/US
  • 3Department Of Oncology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 4Medical Oncology, St Vincents University Hospital, Dublin/IE
  • 5School Of Medicine, University of Torino School of Medicine, Torino/IT
  • 6Oncology, Allina Health System, Minneapolis/US
  • 7Division Of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 8Digestive Endoscopy, Institute Jules Bordet, Brussels/BE
  • 9Cancer, Duke Cancer Institute, Durham/US
  • 10Department Of Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 11Royal Melbourne Hospital, The University of Melburne, Melbourne/AU
  • 12Oncology, Tasman Oncology Research Pty Ltd, Southport/AU
  • 13Global Clinical Research, Oncology, Bristol-Myers Squibb, Princeton/US
  • 14Biostatistics, Bristol-Myers Squibb, Princeton/US
  • 15Oncologie Médicale, Hopital St. Antoine, 75571 - Paris/FR



Globally, about 10% of new cancers each year are CRC and ∼15% of these are MSI-H. Nivolumab (N), a fully human anti-PD-1 mAb, and ipilimumab (I), a humanized anti-CTLA-4 mAb, are immune checkpoint inhibitors with favorable safety and efficacy profiles in multiple tumor types. This phase 2 study evaluates N ± I in MSI-H and non-MSI-H pts with mCRC.


MSI-H pts received N 3 mg/kg q2 wk (N3) or N 3 mg/kg + I 1 mg/kg q3 wk (N3 + I1) x 4 doses followed by N3 until disease progression (PD) or other discontinuation. Initial evaluation of N + I was also completed in non-MSI-H pts. Primary endpoint was investigator-reported ORR by RECIST 1.1. Other endpoints included safety, OS, PFS, and clinical activity in biomarker-defined subpopulations (KRAS, BRAF status, and PD-L1).


70 (N3) and 30 (N3 + I1) MSI-H pts and 3 (N1 + I1), 10 (N1 + I3), and 10 (N3 + I1) non-MSI-H pts were enrolled. All non-MSI-H pts and 87% (N3) and 93% (N3 + I1) of MSI-H pts had ≥2 prior regimens. 47 (67%; N3) and 18 (60%; N3 + I1) MSI-H pts remain on tx. Efficacy data for MSI-H pts are shown in the Table. Responses were also seen in non-MSI-H pts. Median (95% CI) PFS across all non-MSI-H pts was 1.4 mo (1.2, 1.9). Responses were observed regardless of tumor PD-L1 expression. Treatment-related adverse events (TRAEs) occurred in 41 (59%; N3) and 25 (83%; N3 + I1) MSI-H pts; 10 (14%; N3) and 8 (27%; N3 + I1) pts had Grade 3–4 TRAEs. One pt on N3 had a Grade 5 TRAE (sudden death). Additional biomarker data including MSI assessment and influence of BRAF/KRAS mutations will be presented.

MSI-Ha efficacy

N3 (n = 70) N3 + I1 (n = 30)
ORR, n (%)b 12 (25.5) 9 (33.3)
CR PR SD PD Not determined/not reported 0 12 (25.5) 14 (29.8) 17 (36.2) 4 (8.5) 0 9 (33.3) 14 (51.9) 3 (11.1) 1 (3.7)
Median DOR (95% CI), mo NR (4.2, NE) NR (NE, NE)
PFS rates, % (95% CI) 6 mo 9 mo 12 mo 45.9 (29.8, 60.7) 45.9 (29.8, 60.7) 45.9 (29.8, 60.7) 66.6 (45.5, 81.1) NR NR
OS rates, % (95% CI) 6 mo 9 mo 12 mo 75.0 (58.5, 85.7) 65.6 (48.0, 78.6) 65.6 (48.0, 78.6) 85.1 (65.0, 94.2) 85.1 (65.0, 94.2) NR
Baseline PD-L1 expression, n (%) ≥1%


N ± I demonstrated promising clinical activity with a favorable overall safety profile in pts with mCRC, regardless of tumor PD-L1 expression. Additional biomarker analyses are ongoing.

Clinical trial identification

Legal entity responsible for the study

Sponsored by Bristol-Myers Squibb


Sponsored by Bristol-Myers Squibb


H-J. Lenz: Has served as a consultant/advisory board member and received travel expenses from Bayer, Merck Serono, and Roche. He has received honoraria from Bayer, Boehringer Ingelheim, Celgene, Merck Serono, and Roche. P. Garcia-Alfonso: Has served on advisory boards for Roche, Merck, Sanofi, Amgen, Bayer, and Lilly. A. Hill: Is employed by, owns stock in, and has received research funding from Tasman Oncology Research. He has received travel accommodations/expenses from BMS. R.A. Moss: Is employed by and owns stock in Bristol-Myers Squibb. M.V. Goldberg, C-S. Lin, H. Tang: Is an employee of Bristol-Myers Squibb. T. André: Has received honoraria from BMS and consultant fees from Roche. All other authors have declared no conflicts of interest.