Safety and clinical activity of a new anti-PD-L1 antibody as monotherapy or combined with targeted therapy in advanced solid tumors: The PACT phase Ia/Ib trial

Amita Patnaik, Timothy A. Yap, Hyun Cheol Chung, Maria J. de Miguel, Yung Jue Bang, Chia Chi Lin, Wu Chou Su, Antoine Italiano, Kay Hoong Chow, Anna M. Szpurka, Danni Yu, Yumin Zhao, Michelle Carlsen, Shelly Schmidt, Burkhard Vangerow, Leena Gandhi, Xiaojian Xu, Johanna Bendell

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

Purpose: This phase Ia/Ib PACT study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of a new programmed cell death ligand 1 (PD-L1) inhibitor, LY3300054, as monotherapy or in combination with ramucirumab, abemaciclib, or merestinib (a type II MET kinase inhibitor) in patients with advanced, refractory solid tumors (NCT02791334). Patients and Methods: Patients were enrolled into cohorts of escalating LY3300054 dose (phase Ia) as monotherapy (N ¼ 15) or combined with ramucirumab (N ¼ 10), abemaciclib (N ¼ 24), or merestinib (N ¼ 12). The phase Ib dose expansion enrolled 8 patients with melanoma in the monotherapy arm and 12 patients with pancreatic cancer in the merestinib combination arm. Combination treatments were administered concurrently from day 1 of each cycle. A 14-day lead-in abemaciclib arm was also explored. Primary endpoints were dose-limiting toxicity (DLT) and safety. Results: Treatment-related adverse events included fatigue and nausea in the monotherapy arm (13% for each), hypothyroidism (30%) in the ramucirumab arm, diarrhea (54%) in the abemaciclib arm, and nausea (25%) in the merestinib arm. DLTs associated with hepatoxicity were observed in 3 of 4 patients in the abemaciclib lead-in cohorts. No DLTs or grade 3 or 4 hepatoxicity were reported in the concurrent abemaciclib arm. Pharmacokinetic characteristics were comparable with other PD-L1 inhibitors. One patient in each arm experienced a partial response per RECIST v1.1 lasting ≥7 months. Conclusions: LY3300054 was well tolerated without unexpected safety concerns when administered alone or concurrently with ramucirumab, abemaciclib, or merestinib. Lead-in abemaciclib before combining with LY3300054 was not feasible due to hepatotoxicity. Durable clinical benefits were seen in all regimens.

原文English
頁(從 - 到)1267-1277
頁數11
期刊Clinical Cancer Research
27
發行號5
DOIs
出版狀態Published - 2021 三月 1

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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