Clin Cancer Res. 2020 Nov 4:clincanres.1830.2020. doi: 10.1158/1078-0432.CCR-20-1830. Online ahead of print.
PURPOSE: This phase 1/2a study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist immunoglobulin G1 monoclonal antibody, ± nivolumab and/or ipilimumab in patients with advanced solid tumors.
EXPERIMENTAL DESIGN: Patients (with non-small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20-320 mg) ± nivolumab (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 2 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 1 of 20 patients (5%) receiving BMS-986178 monotherapy, 6 of 79 (8%) receiving BMS-986178 plus nivolumab, 0 of 2 receiving nivolumab monotherapy, 6 of 41 (15%) receiving BMS-986178 plus ipilimumab, and 3 of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the maximum tolerated dose 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.
CONCLUSION: 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.