OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors
Gutierrez, Martin; Moreno, Victor; Heinhuis, Kimberley M; Olszanski, Anthony J; Spreafico, Anna; Ong, Michael; Chu, Quincy S; Carvajal, Richard D; Trigo, José; Ochoa de Olza, Maria; Provencio, Mariano; De Vos, Filip; de Braud, Filippo; Leong, Stephen; Lathers, Deanne; Wang, Rui; Ravindran, Palani; Feng, Yan; Aanur, Praveen; Melero, Ignacio
(2021) Clinical cancer research : an official journal of the American Association for Cancer Research, volume 27, issue 2, pp. 460 - 472
(Article)
Abstract
PURPOSE: This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors. PATIENTS AND METHODS: Patients (with non-small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20-320 mg) ± nivolumab
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(240-480 mg) and/or ipilimumab (1-3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, and antitumor activity per RECIST version 1.1. RESULTS: Twenty patients received BMS-986178 monotherapy, and 145 received combination therapy in various regimens (including two patients receiving nivolumab monotherapy). With a follow-up of 1.1 to 103.6 weeks, the most common (≥5%) treatment-related adverse events (TRAEs) included fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. Overall, grade 3-4 TRAEs occurred in one of 20 patients (5%) receiving BMS-986178 monotherapy, six of 79 (8%) receiving BMS-986178 plus nivolumab, zero of two receiving nivolumab monotherapy, six of 41 (15%) receiving BMS-986178 plus ipilimumab, and three of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the MTD was not reached in either the monotherapy or the combination escalation cohorts. No objective responses were seen with BMS-986178 alone; objective response rates ranged from 0% to 13% across combination therapy cohorts. CONCLUSIONS: In this study, BMS-986178 ± nivolumab and/or ipilimumab appeared to have a manageable safety profile, but no clear efficacy signal was observed above that expected for nivolumab and/or ipilimumab.
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Keywords: Oncology, Cancer Research, Journal Article
ISSN: 1078-0432
Publisher: American Association for Cancer Research Inc.
Note: Funding Information: during the conduct of the study; grants and nonfinancial support from Bristol Myers Squibb, MSD, Roche, and Takeda outside the submitted work. F. De Vos reports grants from AbbVie, BioClin Therapeutics, Bristol Myers Squibb, Glaxo Smith Kline, Novartis, Onctimed Oncology BV, and Vaximm outside the submitted work. F. de Braud reports personal fees from Tiziana Life Sciences, Bristol Myers Squibb, Celgene, Servier, Daiichy Sankyo, Ignyta, Novartis, Amgen, Pfizer, Octimet Oncology, Incyte, Pierre Fabre, Eli Lilly, Roche, AstraZeneca, Gentili, Dephaforum, MSD, Bayer, and Fondazione Menarini outside the submitted work. S. Leong reports personal fees from Bristol Myers Squibb and other from Merck outside the submitted work. D. Lathers reports other from Bristol Myers Squibb outside the submitted work. Y. Feng reports nonfinancial support from Bristol Myers Squibb outside the submitted work. P. Aanur reports employment with Bristol Myers Squibb. I. Melero reports grants and personal fees from Bristol Myers Squibb during the conduct of the study; grants and personal fees from Roche, Alligator, F-Star, Bioncotech, AstraZeneca, and Genmab; grants from Numab, Tusk, and Merck Serono outside the submitted work. No disclosures were reported by the other authors. Funding Information: M. Gutierrez reports other from Bristol Myers Squibb during the conduct of the study and personal fees from Merck, Bristol Myers Squibb, COTA, Guardant 360, Esanex, Foundation One, and Eli Lilly outside the submitted work. V. Moreno reports personal fees from Bristol Myers Squibb, Janssen, and Bayer outside the submitted work. A.J. Olszanski reports other from Bristol Myers Squibb during the conduct of the study and personal fees from Merck, Bristol Myers Squibb, Pfizer, Array, EMD Serono, Iovance, Novartis, and Alkermes outside the submitted work. A. Spreafico reports other from Bristol-Myers Squibb, Merck, Novartis, Roche, Alkermes, Surface Oncology, Symphogen, AstraZeneca/Medimmune, Janssen Oncology/Johnson & Johnson, GSK, and Bayer outside the submitted work. M. Ong reports personal fees from Bristol Myers Squibb, Merck, and EMD-Serono and grants and personal fees from AstraZeneca outside the submitted work. Q.S. Chu reports grants and personal fees from AstraZeneca; personal fees from Bristol Myers Squibb, Eli Lilly, Boeringher Ingelheim, Merck, Novartis, Pfizer, and Roche; other from Merck KgaA outside the submitted work. R.D. Carvajal reports personal fees and other from Bristol Myers Squibb during the conduct of the study; personal fees from Castle Biosciences, TriSalus, PureTech Health, Pierre Fabre; personal fees and other from Regeneron, Sanofi Genzyme, Merck, InxMed, and Immunocore; other from Plexxikon, Novartis, Mirati, Astellis, Amgen outside the submitted work; and is a scientific advisory board member at Rgenix, Aura Biosciences, and Chimeron. J. Trigo reports grants from AstraZeneca, Bristol Myers Squibb, Roche, and MSD outside the submitted work. M. Provencio reports grants and nonfinancial support from Bristol Myers Squibb Publisher Copyright: © 2020 American Association for Cancer Research.
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