Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, Tennessee.
HealthPartners Institute, Regions Cancer Care Center, St. Paul, Minnesota.
Clin Cancer Res. 2022 Jun 13;28(12):2517-2526. doi: 10.1158/1078-0432.CCR-21-3009.
ARRY-382 (PF-07265804) is a selective inhibitor of colony-stimulating factor-1 receptor. We evaluated the safety and preliminary efficacy of ARRY-382 plus pembrolizumab in patients with advanced solid tumors.
This was an open-label, multicenter, Phase 1b/2 study (NCT02880371) performed over September 1, 2016 to October 24, 2019. In the Phase 1b dose-escalation, patients with selected advanced solid tumors received ARRY-382 [starting dose 200 mg once daily (QD) orally] plus pembrolizumab [2 mg/kg intravenously (IV) every 3 weeks (Q3W)]. Phase 2 patients had: Pancreatic ductal adenocarcinoma (PDA); programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) inhibitor-refractory (PD-1/PD-L1 IR) advanced solid tumors; or platinum-resistant ovarian cancer (prOVCA). Patients received ARRY-382 at the maximum tolerated dose (MTD) of 300 mg QD plus pembrolizumab 200 mg IV Q3W.
Primary endpoints of dose-limiting toxicities (DLT; Phase 1b) and objective response rate (Phase 2) were met. In Phase 1b, 19 patients received ARRY-382 200-400 mg. Three patients reported DLTs. The MTD of ARRY-382 (plus pembrolizumab) was 300 mg QD. In Phase 1b, 2 patients (10.5%) had confirmed partial response (PR): 1 with PDA and 1 with ovarian cancer, lasting 29.2 and 3.1 months, respectively. In Phase 2, there were 27, 19, and 11 patients in the PDA, PD-1/PD-L1 IR, and prOVCA cohorts, respectively. One patient (3.7%) with PDA had a PR lasting 2.4 months. The most frequent ARRY-382-related adverse events were increased transaminases (10.5%-83.3%) and increased creatine phosphokinase (18.2%-50.0%).
Although limited clinical benefit was observed, ARRY-382 plus pembrolizumab was well tolerated.
ARRY-382（PF-07265804）是一种集落刺激因子-1 受体的选择性抑制剂。我们评估了 ARRY-382 联合 pembrolizumab 治疗晚期实体瘤患者的安全性和初步疗效。
这是一项开放标签、多中心的 1b/2 期研究（NCT02880371），于 2016 年 9 月 1 日至 2019 年 10 月 24 日进行。在 1b 期剂量递增中，选择的晚期实体瘤患者接受 ARRY-382[起始剂量 200 mg 每日一次（QD）口服]联合 pembrolizumab[2 mg/kg 静脉注射（IV）每 3 周（Q3W）]。2 期患者为：胰腺导管腺癌（PDA）；程序性死亡蛋白-1（PD-1）/PD-配体 1（PD-L1）抑制剂难治（PD-1/PD-L1 IR）的晚期实体瘤；或铂耐药卵巢癌（prOVCA）。患者接受 ARRY-382 最大耐受剂量（MTD）300 mg QD 联合 pembrolizumab 200 mg IV Q3W。
剂量限制性毒性（DLT；1b 期）和客观缓解率（2 期）的主要终点达到。在 1b 期，19 名患者接受了 ARRY-382 200-400 mg。3 名患者报告了 DLTs。 ARRY-382（加 pembrolizumab）的 MTD 为 300 mg QD。在 1b 期，2 名患者（10.5%）有确认的部分缓解（PR）：1 名 PDA 患者和 1 名卵巢癌患者，分别持续 29.2 和 3.1 个月。在 2 期，PDA、PD-1/PD-L1 IR 和 prOVCA 队列分别有 27、19 和 11 名患者。1 名 PDA 患者（3.7%）的 PR 持续 2.4 个月。最常见的 ARRY-382 相关不良事件为氨基转移酶升高（10.5%-83.3%）和肌酸磷酸激酶升高（18.2%-50.0%）。
尽管观察到有限的临床获益，但 ARRY-382 联合 pembrolizumab 耐受性良好。
