Santoro, Armando, Assenat, Eric, Yau, Thomas, Delord, Jean-Piere, Maur, Michela, Knox, Jennifer, Cattan, Stephane, Lee, Kyung-Hun, Del Conte, Gianluca, Springfield, Christoph, Leo, Elisa, Xyrafas, Alexandros, Fairchild, Lauren, Mardjuadi, Feby Ingriani and Chan, Stephen (2024) A phase 1b/2 trial of capmatinib plus spartalizumab or spartalizumab alone in patients with pretreated hepatocellular carcinoma. JHEP Reports.

Abstract

Background & Aims: This phase 1b/2 trial evaluated the safety and efficacy of capmatinib in combination with spartalizumab or spartalizumab alone in patients with advanced hepatocellular carcinoma (HCC).
Methods: Eligible patients who had progressed or were intolerant to sorafenib received escalating doses of capmatinib 200 mg, 300 mg, and 400 mg bid plus spartalizumab 300 mg q3w in phase 1b. Once the recommended phase 2 dose (RP2D) was declared, phase 2 commenced with randomization 1:1 to treatment with either capmatinib + spartalizumab (n = 32) or spartalizumab alone (n = 30). Primary endpoints were safety and tolerability (phase 1b); and investigator-assessed ORR per RECIST v1.1 for combination versus single-agent arms using a Bayesian logistic regression model (phase 2).
Results: In phase 1b, the RP2D for capmatinib in combination with spartalizumab was determined as 400 mg bid. Dose-limiting toxicity of grade 3 diarrhea was reported in 1 patient in the capmatinib 400 mg bid + spartalizumab 300 mg q3w dose level. The primary endpoint in phase 2 was not met. The observed ORR in the capmatinib + spartalizumab arm was 9.4% versus 10% in the spartalizumab arm. The most common any-grade treatment-related adverse events (TRAEs ≥20%) were nausea (37.5%), asthenia and vomiting (28.1% each), diarrhea, pyrexia, and decreased appetite (25.0% each) in the combination arm; TRAEs ≥10% were pruritus (23.3%) and rash (10.0%) in the spartalizumab-alone arm.
Conclusion: Capmatinib at 400 mg bid plus spartalizumab 300 mg q3w was established as the RP2D, with manageable toxicities and no significant safety signals, but the combination did not show superior clinical activity compared to spartalizumab single-agent treatment in patients with advanced HCC who had been previously treated with sorafenib.

Item Type:	Article
Keywords:	Capmatinib, Spartalizumab, hepatocellular carcinoma, MET, PD-1
Date Deposited:	14 Feb 2024 00:45
Last Modified:	14 Feb 2024 00:45
URI:	https://oak.novartis.com/id/eprint/52753