Abstract 1694
Background
Pembro, a PD-1 inhibitor, confers durable benefit in many tumor types but has limited efficacy in non–microsatellite instability–high (MSI-high)/pMMR mCRC. Chemotherapies that include 5-fluorouracil (5-FU), oxaliplatin and irinotecan, which are commonly used to treat mCRC, may modulate intrinsic tumor immunogenicity and sensitize tumors to immunotherapy agents. In the phase 1b KEYNOTE-651 study (NCT03374254), pembro + mFOLFOX7 (cohort B) or pembro + FOLFIRI (cohort D) was evaluated in patients with non–MSI-high/pMMR mCRC.
Methods
Patients were ≥18 years with non–MSI-high/pMMR mCRC, Eastern Cooperative Oncology Group performance status 0/1, and no prior systemic chemotherapy for stage IV mCRC (cohort B) or 1 prior therapy including a fluoropyrimidine + oxaliplatin-based regimen (cohort D). Patients received pembro 200 mg every 3 weeks (Q3W) + mFOLFOX7 (oxaliplatin [85 mg/m2]; leucovorin [400 mg/m2]; 5-FU [2400 mg/m2]) Q2W (cohort B) or pembro 200 mg Q3W + FOLFIRI (irinotecan [180 mg/m2]; leucovorin [400 mg/m2]; 5-FU [2400 mg/m2]) Q2W (cohort D). Primary objectives were safety/tolerability and establishment of the recommended phase 2 dose (RP2D); the secondary objective was objective response rate.
Results
At data cutoff (Feb 18, 2019), 15 patients in cohort B and 16 in cohort D started treatment; median follow-up was 6.8 months (cohort B) and 5.7 months (cohort D). Treatment was discontinued in 4 patients (27%) in cohort B (adverse event [AE], n = 1 [7%]; PD, n = 3 [20%]) and 9 patients (56%) in cohort D (AEs, PD, patient withdrawal; n = 3 [19%] each). There was 1 dose-limiting toxicity in cohort D: grade 3 small-intestinal obstruction. See RP2Ds for cohorts B and D in the Methods section. All patients had ≥1 treatment-related AE (TRAE). Grade 3 TRAEs occurred in 8 patients each in cohort B (53%) and cohort D (50%), most commonly anemia and neutropenia (13% each) in cohort B and neutropenia, diarrhea, fatigue, and leukopenia (13% each) in cohort D. There were no grade 4-5 TRAEs. Efficacy results will be presented.
Conclusions
Pembro in combination with mFOLFOX7 or FOLFIRI was safe and tolerable in patients with mCRC.
Clinical trial identification
NCT03374254; Release date: December 15, 2017.
Editorial acknowledgement
Jacqueline Kolston, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA); Funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Array BioPharma.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Array BioPharma.
Disclosure
R. Kim: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Research grant / Funding (institution): Eisai. J. Kortmansky: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche. L. Wong: Research grant / Funding (institution): Astellas Pharma Global Development, Inc./Astellas US, Inc.; Research grant / Funding (institution): BeiGene, Ltd; Research grant / Funding (institution): Exelixis, Inc.; Research grant / Funding (institution): Merck; Research grant / Funding (institution): NovoCure, Inc.; Research grant / Funding (institution): Pierre Fabre Médicament; Research grant / Funding (institution): PledPharma AB; Research grant / Funding (institution): SynCore Biotechnology Co., Ltd.; Research grant / Funding (institution): Halozyme, Inc.; Research grant / Funding (institution): Pharmacyclics, Inc.; Research grant / Funding (institution): TESARO; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Array. M. Tehfe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self): Ipsen; Advisory / Consultancy: BMS; Advisory / Consultancy: Takeda; Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Taisho. J.J. Li: Full / Part-time employment: Merck & Co., Inc. M. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. C. Mayo: Full / Part-time employment: Merck & Co., Inc. P. Marinello: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. E. Chiorean: Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Halozyme; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Array; Advisory / Consultancy: Five Prime; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Halozyme; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Ignyta/Roche; Research grant / Funding (institution): Stemline; Research grant / Funding (institution): Macrogenetics. All other authors have declared no conflicts of interest.
Resources from the same session
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract
908 - Romidepsin (FK228) Regulates the Expression of the Immune Checkpoint Ligand PD-L1 and Exerts Synergistic Anti-Tumor Activity with an Anti-PD-1 Antibody in Colon Cancer
Presenter: Hui Li
Session: Poster Display session 2
Resources:
Abstract
3127 - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first line chemotherapy.
Presenter: Zafeiris Zafeiriou
Session: Poster Display session 2
Resources:
Abstract
5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer
Presenter: Camilla Lisanti
Session: Poster Display session 2
Resources:
Abstract
2518 - SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: analysis of the metastatic colorectal cancer patients in the dose escalation phase
Presenter: Marwan Fakih
Session: Poster Display session 2
Resources:
Abstract
4000 - Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
Presenter: Niels Halama
Session: Poster Display session 2
Resources:
Abstract
2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer
Presenter: Wataru Okamoto
Session: Poster Display session 2
Resources:
Abstract
2569 - Phase II trial of Trametinib (T) and Panitumumab (Pmab) in RAS/RAF wild type (wt) metastatic colorectal cancer (mCRC)
Presenter: Kanan Alshammari
Session: Poster Display session 2
Resources:
Abstract
5402 - Microsatellite instability and immunogenicity in colorectal cancer – do resident memory Tcells (Trm) play a role in colorectal cancer
Presenter: Wei Toh
Session: Poster Display session 2
Resources:
Abstract
5472 - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Presenter: Camilla Qvortrup
Session: Poster Display session 2
Resources:
Abstract