OX40 Agonist BMS-986178 Phase1/2a Trial Results

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors

In a recent article from the AACR’s Clinical Cancer Research journal, January 2021, investigators reported on the phase 1–2a clinical trial evaluating the safety and activity of BMS–986178, a fully human OX40 IgG1 monoclonal antibody agonist with or without nivolumab and/or ipilimumab in a variety of metastatic solid tumors. 

BMS–986178 was administered between 20 – 320 mg in combination with nivolumab 240 or 480 mg and/or ipilimumab 1 to 3 mg/kg. Safety was the primary endpoint. Other endpoints included not only pharmacokinetics and pharmacodynamics, but also immunogenicity and antitumor activity. Antitumor activity was determined through the RECIST version 1.1 criteria.

Of the 165 patients on the trial, 20 patients received BMS–986178 monotherapy while 145 received combination therapy with various regimens. The follow-up range was between 1.1 and 104 weeks. The most common adverse events included fatigue, pruritus, rash, pyrexia, diarrhea as well as infusion related reactions. 5% of patients had grade 3 or 4 treatment-related adverse events with BMS–986178 monotherapy, 8% with BMS–986178 plus nivolumab, 0% with nivolumab monotherapy, 15% with BMS-986178 plus ipilimumab, and 13% receiving BMS–986178 plus nivolumab and ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy. The maximum tolerated dose was not achieved in combination therapy. No objective responses were seen with monotherapy, and the objective response rates range from 0% to 13% across the combination cohorts.

The authors concluded that despite the manageable side effect profile, BMS–986178 given as monotherapy or in combination with nivolumab with or without ipilimumab , provided no efficacy signal.