Robin Kate Kelley, MD gives an overview of a presentation from ASCO 2020 entitled Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC).
In the initial cohort of this study (NCT02519348), the combination of double immune control point inhibitors (ICI) T (anti – CTLA-4) and D (anti – PD-L1) showed tolerability with positive objective response rate (ORR). Subsequent assessment of pts with solid tumors treated with can doses of T indicated priming with a higher dose of T can induce a stronger immune response and improve anti-tumor activity. The randomized expansion cohorts thus included 4 arms testing T and D as monotherapies and 2 T+D schemes, including a novel T+D scheme with a single priming dose of T.
T300+D (T 300 mg + D 1500 mg 1 dose followed by D Q4 weekly [Q4W]) or T75+D (T 75 mg Q4W + D 1500 mg Q4W [4 dose] followed by D Q4W) or T75+D (T 75 mg Q4W + D 1500 mg Q4W [4 dose] followed by D Q4W); or single agent D (1500 mg Q4W) or T (750 mg Q4W). Primary endpoint was safety. The ORR was evaluated by blinded, unbiased central review using RECIST v1.1, response length (DoR), circulating lymphocytes, and overall survival ( OS).
332 pts were inscribed at the data cut-off (09/02/2019). Median follow-ups for T300+D were 11.7 months (mo); 14.6 (T75+D), 8.9 (D), and 15.8 (T). Incidences of the treatment-related adverse event (trAE) are shown (Table); no deaths for T300+D or T were due to trAEs. The T300+D arm had the highest reported ORR (DoR did not hit [NR]) and the longest operating system (Table). The T300+D arm established a distinct proliferative T cell profile for pts, indicating additive biological activity for the combination, and showed high cytotoxic (CD8) counts of pts with an OR.
The supporting clinical activity and the tolerable safety profile suggest that T300+D offers the better benefit-risk balance versus T75+D or monotherapy. The T300+D regimen 's unusual pharmacodynamic behavior further supports its usage in aHCC. In the ongoing step III HIMALAYA analysis (NCT03298451) for first-line HCC vs sorafenib, T300+D and D are being evaluated. Credit: AstraZeneca. Details on clinical trials: NCT02519348.