Updated safety and efficacy results from the phase I study of either LBL-007 (an anti-LAG-3 antibody) in combination with toripalimab (an anti-PD-1 antibody) or LBL-007 in combination with toripalimab and axitinib in patients with advanced melanoma.

Abstract

9541 Background: Initial safety and efficacy data of LBL-007 plus toripalimab in patients with advanced melanoma (Part A) have been reported in 2022 ASCO (Abstract 9538). Here we present the updated results of part A and the preliminary results of part B (LBL-007 plus toripalimab with axitinib). Median follow-up was 9.7 months at cut-off data (January 11, 2023). Methods: Patients with advanced melanoma with or without prior therapy were enrolled during Jan 2021 - Aug 2022. This trial comprised 2 parts: Part A, patients received LBL-007 (0.25 - 10 mg/kg for dose escalation; 3 or 6 mg/kg for dose expansion) plus toripalimab at 3 mg/kg (both i.v. Q2W); and Part B, patients received LBL-007 at 3 or 6 mg/kg plus toripalimab at 3 mg/kg (both i.v. Q2W) and axitinib at 5 mg BID. The primary objective was safety, the second objectives were pharmacokinetics, pharmacodynamics and efficacy (per RECIST v.1.1). Results: In part A, 68 patients in total (57 treatment-naïve) were enrolled including 20 patients in dose escalation and 48 patients in dose expansion, and among which, 31 additional patients have been enrolled since 2022 ASCO report. Nineteen (27.9%) patients occurred grade ≥3 TEAEs, the common grade ≥3 TEAEs was anaemia (11.8%). No new safety signals were detected. Among 55 efficacy evaluable treatment-naïve patients (41 with acral, 7 mucosal, 7 others), ORR was 23.6%, DCR was 58.2%, and mPFS was 5.7 months (95% CI: 3.7, 9.5). In part B, 11 patients (10 mucosal, 1 acral) were enrolled. No DLT was observed. Five patients (45.5%) occurred grade ≥3 TEAEs, the common grade ≥3 TEAEs included blood pressure increased (18.2%) and transaminases increased (18.2%). One (9.1%) patient discontinued treatment due to TEAEs. ORR was 45.4% (including 4 mucosal and 1 acral), DCR was 72.7%, and mPFS was 5.5 months (95% CI: 1.8, 9.1). Conclusions: LBL-007 plus toripalimab continued to show promising antitumor activity and manageable safety profile in patients with treatment-naïve melanoma, which support further development in this indication. LBL-007/toripalimab/axitinib combination demonstrated acceptable safety profile and encouraging antitumor activity in patients with mucosal melanoma. Acknowledgements: Junshi Biosciences. Clinical trial information: NCT04640545 .