OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors
OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors
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DOI：
10.1158/1078-0432.ccr-20-1830
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发表时间：
2021-01-15
影响因子：
11.5
通讯作者：
Melero, Ignacio
中科院分区：
文献类型：
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作者：
Gutierrez, Martin;Moreno, Victor;Melero, Ignacio
目的：这项I/IIa期研究（NCT 02737475）评价了BMS-986178（一种全人0X 40激动剂IgG 1 mAb）、+/-纳武单抗和/或伊匹单抗在晚期实体瘤患者中的安全性和活性。患者（非小细胞肺，肾细胞，膀胱，其他晚期癌症）接受BMS-986178（20-320 mg）+/-纳武单抗（240-480 mg）和/或伊匹单抗（1-3 mg/kg）。主要终点是安全性。其他终点包括免疫原性、药效学、药代动力学和抗肿瘤活性（根据RECIST 1.1版）。结果：20例患者接受BMS-986178单药治疗，145例患者接受各种方案的联合治疗（包括2例接受纳武单抗单药治疗的患者）。随访1.1 - 103.6周，最常见（>= 5%）的治疗相关不良事件（TRAE）包括疲劳、瘙痒、皮疹、发热、腹泻和输注相关反应。总体而言，接受BMS-986178单药治疗的20例患者中有1例（5%）发生3-4级TRAE，接受BMS-986178加纳武单抗治疗的79例患者中有6例（8%）发生TRAE，接受纳武单抗单药治疗的2例患者中有0例发生TRAE，接受BMS-986178加伊匹单抗治疗的41例患者中有6例（15%）发生TRAE，以及接受BMS-986178加纳武单抗加伊匹单抗的23例中的3例（13%）。未发生死亡。单药治疗未观察到剂量限制性毒性，单药治疗或联合递增队列均未达到MTD。结论：在这项研究中，BMS-986178 +/-纳武单抗和/或伊匹单抗似乎具有可管理的安全性特征，但没有观察到高于纳武单抗和/或伊匹单抗预期的明确疗效信号。
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 (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 followup 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.