Résumé
Background: TRIPLET-HCC is a French, multicentre, randomized 1:1, open-label phase II-III trial designed to evaluate efficacy and safety of the triple combination (Arm-A) by the addition of ipilimumab (1 mg/kg for the first 4 cycles) to atezolizumab/bevacizumab (Q3W), versus the double atezolizumab/bevacizumab combination (Arm-B) for HCC eligible to systemic therapy in first line setting. The primary objective of phase II is the objective response rate in Arm-A, and overall survival in Arm-A versus Arm-B in phase III. In phase II, the first 15 pts randomized in Arm-A were assessed for a safety-run in aim to detect a potential signal of overtoxicity after the first four cycles of triple therapy (induction phase), thus allowing or forbidding the continuation of the trial. Methods: The trial started on March 2023 the 9 th . Adverse events (AE) and their imputability to treatment were reported in the eCRF by investigators. An independent data safety monitoring board (DSMB) was gathered 4 weeks after the last injection of ipilimumab of the 5 th and the 15 th patient randomized in Arm-A of phase II. The second DSMB meeting took place on November 2023 after extraction of data in November 2023 the 9 th . These data are presented in the present abstract. Results: At the DSMB meeting date, 15 patients in Arm-A were analyzed for safety while 13 patients had been randomized in Arm-B and had reached at least 4 cycles of treatment. In Arm-A, 12 pts completed the first 4 cycles of triple therapy, 1 pt received 3 cycles (sepsis), 1 pt only 2 (prednisone > 10 mg/day for grade-1 myocarditis which recovered), and 1 pt only 1 (sepsis and death). In Arm-B, 11 pts received the first 4 cycles of double therapy, 2 pts only 3 (anemia, lithiasic cholangitis). Three deaths occurred: 2 in Arm-A (1 possible related to immune-related (iR) hepatitis (not biopsy-proven) associated with sepsis, and 1 sudden death of unknow etiology), and one in Arm-B (tumor progression). Three pts in Arm-A (2 radiologic progressions, 1 death) and 1 pt in Arm-B (1 tumor progression with death) were withdrawn of the trial. Regarding grade-3/4 treatment-related adverse events (TRAE), 3 were reported in Arm-A (1 ASAT increase, 1 arterial hypertension, 1 colitis), and 2 in Arm-B (1 tumor bleeding, 1 arterial hypertension). Conclusions: The preliminary safety data from the TRIPLET-HCC trial suggest that the triple combination therapy is associated with a manageable safety profile, showing no unexpected signs of over toxicity. The DSMB's decision to continue the trial underscores the potential of this innovative therapeutic approach in improving outcomes for HCC patients. These findings support further investigation into the efficacy and long-term safety of the triple combination therapy in a broader patient population. Clinical trial information: NCT05665348 .