RT Journal Article
T1 OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors.
A1 Gutierrez, Martin
A1 Moreno, Victor
A1 Heinhuis, Kimberley M
A1 Olszanski, Anthony J
A1 Spreafico, Anna
A1 Ong, Michael
A1 Chu, Quincy
A1 Carvajal, Richard D
A1 Trigo, José
A1 Ochoa de Olza, Maria
A1 Provencio, Mariano
A1 De Vos, Filip Yves
A1 De Braud, Filippo
A1 Leong, Stephen
A1 Lathers, Deanne
A1 Wang, Rui
A1 Ravindran, Palani
A1 Feng, Yan
A1 Aanur, Praveen
A1 Melero, Ignacio
AB 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 (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.
YR 2020
FD 2020-11-04
LK https://hdl.handle.net/10668/26690
UL https://hdl.handle.net/10668/26690
LA en
DS RISalud
RD Apr 7, 2025