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 sessionZUMA-3: A phase 1/2 multi-center study evaluation the safety and efficacy of KTE-C19 anti-CD19 CAR T cells in adult patients with relapsed/refractory B precursor acute lymphoblastic leukemia (R/R ALL)Presenter: Bijal Shah Session: Poster display Resources: Abstract ZUMA-2: A phase 2 multi-center study evaluating the efficacy of KTE-C19 (Anti-CD19 CAR T cells) in patients with relapsed/refractory Mantle cell lymphoma (R/R MCL)Presenter: Michael Wang Session: Poster Display Resources: Abstract ZUMA-1: A phase 2 multi-center study evaluating anti-CD19 chimeric antigen receptor (CAR) T cells in patients with refractory aggressive non-Hodgkin lymphoma (NHL)Presenter: Sattva Neelapu Session: Poster Display Resources: Abstract Younger age as a prognostic indicator in breast cancer: Correlation between clinical-pathologic factors and miRNAs and long-term follow-upPresenter: Maria Teresa Martinez Session: Poster display Resources: Abstract Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)Presenter: Christy Toms Session: Poster display Resources: Abstract Whole exome sequencing (WES) and RNA sequencing (RNA-seq) in routine clinical practice for colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) patients (pts)Presenter: Géraldine Perkins Session: Poster display Resources: Abstract What is the optimal annual interpretive volume for a radiologist reading screening mammograms?Presenter: Asli Uluturk Session: Poster display Resources: Abstract What decides breast conservation versus mastectomy in the background of diverse sociocultural environment, an Indian studyPresenter: Poonamalle Padmanabhan Bapsy Session: Poster display Resources: Abstract Waiting time to diagnosis and treatment of the head and neck cancer in four institutions in PortugalPresenter: Ana Castro Session: Poster display Resources: Abstract Wait times for diagnosis and treatment of lung cancer: a single centre experiencePresenter: Catherine Labbe 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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