1. Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Microsatellite Stable Colorectal Cancer.
- Author
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Bessudo A, Haseeb AM, Reeves JA, Zhu X, Wong L, Giranda V, Suttner L, Liu F, Chatterjee M, and Sharma S
- Subjects
- Humans, Female, Middle Aged, Male, Aged, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Microsatellite Instability
- Abstract
Background: Pembrolizumab, a monoclonal antibody against PD-1, has shown limited efficacy in patients with microsatellite stable or mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (CRC). We evaluated vicriviroc (small-molecule C-C motif chemokine ligand 5 antagonist) plus pembrolizumab in patients with advanced or metastatic MSS/pMMR CRC., Patients and Methods: This open-label, phase 2 trial (NCT03631407) enrolled adults with histologically confirmed, locally advanced, unresectable or metastatic CRC that was MSS per local assessment. All patients had received previous treatment with standard therapies. Patients were randomized 1:1 to vicriviroc 150 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or vicriviroc 250 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles (2 years). Primary endpoints were the objective response rate (ORR) as assessed by the investigator per RECIST v1.1, dose-limiting toxicities (DLTs), adverse events (AEs), and discontinuations due to AEs., Results: Forty patients were enrolled and treated. ORR was 5% (95% CI, 0.1%-24.9%) in both treatment groups. There were no complete responses; 1 patient in each treatment group experienced a partial response. No patient in the vicriviroc 150 mg plus pembrolizumab group experienced a DLT. Two patients in the vicriviroc 250 mg plus pembrolizumab group experienced DLTs (1 grade 4 encephalopathy and 1 grade 4 pneumonitis)., Conclusion: The combination of vicriviroc at doses of 150 or 250 mg plus pembrolizumab 200 mg showed limited antitumor activity in patients with advanced or metastatic MSS/pMMR CRC. Toxicity with the combination was manageable., Competing Interests: Disclosure Xiaofu Zhu: Advisory Board—Pfizer, Novartis, Lilly, AstraZeneca, Genomic Health, Apobiologix, Merck & Co., Inc., Rahway, NJ, USA, Leo Pharma, Amgen, and Taiho Pharma. Educational Support – Taiho Pharma and Novartis. Lucas Wong: Research funding to support study conduct from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Vincent Giranda: Former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stockholder in Merck & Co., Inc., Rahway, NJ, USA. Leah Suttner, Fang Liu, and Manash Chatterjee: Employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stockholders in Merck & Co., Inc., Rahway, NJ, USA. Sunil Sharma: Received fees from Barricade Therapeutics, Celularity Inc., Elevar Therapeutics, Incyte, Stemline Therapeutics, Inc., Rappta Therapeutics, Processa Pharmaceuticals, and Novelty Nobility. All other authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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