Nivolumab ± ipilimumab treatment (Tx) efficacy, safety, and biomarkers in patients (Pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): results from the CheckMate-142 study

Date

08 Oct 2016

Session

Poster Display

Presenters

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

Author affiliations

  • 1 Gastrointestinal Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2 Department Of Gastrointestinal (gi) Medical Oncology, Division Of Cancer Medicine, MD Anderson Cancer Center, Houston/US
  • 3 Department Of Oncology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 4 Medical Oncology, St Vincents University Hospital, Dublin/IE
  • 5 School Of Medicine, University of Torino School of Medicine, Torino/IT
  • 6 Oncology, Allina Health System, Minneapolis/US
  • 7 Division Of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 8 Digestive Endoscopy, Institute Jules Bordet, Brussels/BE
  • 9 Cancer, Duke Cancer Institute, Durham/US
  • 10 Department Of Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 11 Royal Melbourne Hospital, The University of Melburne, Melbourne/AU
  • 12 Oncology, Tasman Oncology Research Pty Ltd, Southport/AU
  • 13 Global Clinical Research, Oncology, Bristol-Myers Squibb, Princeton/US
  • 14 Biostatistics, Bristol-Myers Squibb, Princeton/US
  • 15 Oncologie Médicale, Hopital St. Antoine, 75571 - Paris/FR
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Background

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.

Methods

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).

Results

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%

Conclusions

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

Funding

Sponsored by Bristol-Myers Squibb

Disclosure

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.

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