Gutierrez, MartinMoreno, VictorHeinhuis, Kimberley MOlszanski, Anthony JSpreafico, AnnaOng, MichaelChu, QuincyCarvajal, Richard DTrigo, JoséOchoa de Olza, MariaProvencio, MarianoDe Vos, Filip YvesDe Braud, FilippoLeong, StephenLathers, DeanneWang, RuiRavindran, PalaniFeng, YanAanur, PraveenMelero, Ignacio2023-02-092023-02-092020-11-04http://hdl.handle.net/10668/16546This 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 (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. 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. 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.enAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCohort StudiesFemaleHumansIpilimumabMaleMiddle AgedNeoplasmsNivolumabReceptors, OX40Treatment Outcomeresearch article33148673open access10.1158/1078-0432.CCR-20-18301557-3265https://aacrjournals.org/clincancerres/article-pdf/27/2/460/2067217/460.pdf