Safety outcomes with tremelimumab (T) rechallenge in the phase 3 HIMALAYA study of T plus durvalumab (D) in unresectable hepatocellular carcinoma.

Abstract

541 Background: In HIMALAYA (NCT03298451), STRIDE (Single T Regular Interval D) improved overall survival vs sorafenib at the 3-yr and 5-yr data cutoffs (DCOs), with manageable safety. We assess baseline characteristics and safety outcomes in STRIDE-treated HIMALAYA participants (pts) who were T-rechallenged. Methods: Pts were randomized to STRIDE (T 300 mg once + D 1500 mg every 4 weeks [Q4W]), D monotherapy (1500 mg Q4W), or sorafenib (400 mg BID). Pts who, by investigator assessment, were benefitting from STRIDE but had evidence of progressive disease (of target or non-target lesions), could receive one additional dose of T 300 mg after ≥6 cycles of D. Efficacy was not assessed due to implicit survivorship bias in the cohort. In this post-hoc exploratory analysis, baseline characteristics at initial T dosing, treatment (tx) exposure, and safety are assessed in STRIDE-treated pts who were T-rechallenged. Outcomes are assessed at 3 yrs (primary DCO: Aug 27, 2021) and 5 yrs (DCO: Mar 1, 2024) of follow-up. Results: At the 3-yr DCO, 30/393 (8%) pts were T-rechallenged; at the 5-yr DCO, 34/393 (9%) pts were T-rechallenged (64 yrs median age, 85% male, 27% Asian; similar to overall study population). At the 3-yr DCO, the median (range) tx duration of D was 16.5 (5.5–42.6) months (mo) for T-rechallenged pts vs 5.5 (0.4–42.6) mo for all STRIDE pts. At the 5-yr DCO, the median (range) tx duration of D was 16.6 (5.5–72.0) mo for T-rechallenged pts vs 5.5 (0.3–72.0) mo for all STRIDE pts; the median (range) time from tx start to T rechallenge was 12.8 (4.9–53.4) mo; 44% of pts were rechallenged ≤12 mo of starting tx. Overall, T-rechallenged pts had similar safety outcomes to the overall STRIDE population. At the 3-yr DCO, adverse events (AEs) of any causality occurred in 97% of T-rechallenged pts vs 97% of all STRIDE pts (Table). No AEs with outcome of death occurred in T-rechallenged pts. Immune-mediated AEs (imAEs) occurred in 33% of T-rechallenged pts; 10% had imAEs requiring high-dose steroids. Among T-rechallenged pts, 17% had a Grade 3 or 4 treatment-related AE (TRAE) at any time (10% before and 7% after rechallenge). Serious TRAEs occurred in 6% of T-rechallenged pts vs 18% of all STRIDE pts, with no new serious TRAEs between the 3-yr and 5-yr DCOs. Conclusions: Tx was well-tolerated by T-rechallenged pts under the protocol conditions. Despite a limited cohort size, the baseline characteristics and safety outcomes were in line with the overall STRIDE population. Clinical trial information: NCT03298451 . n (%) T-rechallenged pts(n=30*) All STRIDE pts(n=388*) Any AE 29 (96.7) 378 (97.4) Grade 3/4 AE 12 (40.0) 196 (50.5) AE with outcome of death 0 30 (7.7) imAE 10 (33.3) 139 (35.8) Any TRAE 22 (73.3) 294 (75.8) TRAE pre-rechallenge 21 (70.0) - TRAE post-rechallenge 9 (30.0) - Serious TRAE by 3-yr DCO 2 (6.7) 68 (17.5) Serious TRAE by 5-yr DCO 2 (5.9) † 68 (17.5) *In the safety analysis set (all pts who received ≥1 dose of study tx). † n=34 at 5-yr DCO.