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
Journal
Clinical Cancer Research
Journal Volume
27
Journal Issue
5
Pages
1267-1277
Date Issued
2021
Author(s)
Patnaik A.
Yap T.A.
Chung H.C.
de Miguel M.J.
Bang Y.-J.
Su W.-C.
Italiano A.
Chow K.H.
Szpurka A.M.
Yu D.
Zhao Y.
Carlsen M.
Schmidt S.
Vangerow B.
Gandhi L.
Xu X.
Bendell J.
Abstract
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: = 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.
SDGs
Publisher
American Association for Cancer Research Inc.
Type
journal article