Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study
This is the report of a randomized phase 1/2 study assessing the safety and efficacy of tremelimumab (T; anti-CTLA4) and durvalumab (D; anti-PD-L1) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma, previously treated with (or refusing) sorafenib, including a novel regimen with a single, priming dose of tremelimumab. 332 patients were randomized to T300+D (N=75), durvalumab (N=104), tremelimumab (N=69), T75+D (N=84). Tolerability was acceptable, grade ³3 treatment-related adverse events occurred in 37.8%, 20.8%, 43.5%, 24.4%. Confirmed ORRs (95% CI) were 24.0% (14.9-35.3), 10.6% (5.4-18.1), 7.2% (2.4-16.1), 9.5% (4.2-17.9). Median (95% CI) overall survival was 18.7 (10.8-27.3), 13.6 (8.7-17.6), 15.1 (11.3-20.5), 11.3 (8.4-15.0) months, respectively. An early expansion of CD8+ lymphocytes was associated with response, with highest proliferating CD8+ lymphocyte levels in the T300+D arm. The T300+D regimen demonstrated the most encouraging benefit-risk profile and with D monotherapy is being evaluated versus sorafenib in the ongoing phase 3 HIMALAYA study.
(Kelley, R.K. et al. – J Clin Oncol, September 2021)