Abstract 3423
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% ConclusionsN ± 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 identificationLegal entity responsible for the studySponsored by Bristol-Myers Squibb FundingSponsored by Bristol-Myers Squibb DisclosureH-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. Resources from the same session2354 - The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institutionPresenter: Seung Tae Kim Session: Poster Display Resources: Abstract 2594 - Neuroendocrine carcinomas of the colorectal origin - Polish experiencePresenter: Agnieszka Kolasińska-Ćwikła Session: Poster Display Resources: Abstract 2539 - Neuroendocrine neoplasms of the appendix including goblet cell carcinoidsPresenter: Agnieszka Kolasinska-Cwikla Session: Poster Display Resources: Abstract 1245 - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendixPresenter: Amir Mehrvarz Sarshekeh Session: Poster Display Resources: Abstract 3902 - Enhancer of zest homolog 2 (EZH2) expression in well and moderately differentiated pancreatic neuroendocrine tumor (pNET)Presenter: Riccardo Marconcini Session: Poster Display Resources: Abstract 3882 - Differential clinical and pathological characteristics of hereditary neuroendocrine pancreatic tumours (NEPT)Presenter: Gema Marín Zafra Session: Poster Display Resources: Abstract 2296 - Natural course of thyroid cancer nodules compared with benign thyroid nodulesPresenter: Kyung-Jin Yun Session: Poster Display Resources: Abstract 4083 - Reassessment of proliferative activity at disease progression in neuroendocrine neoplasmsPresenter: Noemi Cicchese Session: Poster Display Resources: Abstract 3866 - 18F-FDG-PET to predict disease progression in advanced digestive neuroendocrine neoplasmsPresenter: Maria Rinzivillo Session: Poster Display Resources: Abstract 3651 - UK phase IV, observational study to assess quality of life in patients (pts) with pancreatic neuroendocrine tumours (pNETS) receiving treatment with everolimus: The “real-world” OBLIQUE studyPresenter: John Ramage Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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