Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody toripalimab, in patients with advanced malignant tumors: A phase Ib/II, open-label, multicenter, dose escalation/expansion study

Abstract Background: Dual inhibition of PD-1 and LAG-3 may have the potential to increase the immune response against tumor growth synergistically. Here we report the preliminary safety and efficacy results of LBL-007 (an anti-LAG-3 antibody) in combination with toripalimab (an anti-PD-1 antibody) in patients with advanced malignant tumors. Methods: Patients with advanced malignant tumors, including but not limited to nasopharyngeal carcinoma (NPC), non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), and head and neck squamous carcinoma (HNSCC), with or without prior anti-PD-(L)1 therapy, were enrolled. This trial was divided into two parts: phase Ib (dose escalation study), patients received LBL-007 at 200 mg or 400 mg plus toripalimab at 240 mg (both administered i.v. Q3W), and phase II (dose expansion), patients received LBL-007 at 400 mg and toripalimab at 240 mg (both administered i.v. Q3W). The primary objective was to assess safety and tolerability; the secondary objectives were to assess pharmacokinetics, pharmacodynamics, and preliminary efficacy (per RECIST 1.1). Results: By December 1, 2023, 80 patients were enrolled in phase Ib (10 patients) and phase II (70 patients). Of these, 30 (37.5%) were NPC patients, and 50 (62.5%) had other tumors. The median follow-up was 18.1 months (95% CI: 11.1, NE). No DLTs were observed in phase Ib. Seventy-three patients out of 80 (91.3%) experienced TEAEs of all grades, with 19 (23.8%) having grade ≥3 TEAEs. The most common any grade TEAEs (≥15%) were anaemia (40.0%), hypoalbuminaemia (18.8%), weight decreased (18.8%), hyponatremia (17.5%), proteinuria (17.5%), asthenia (17.5%), lymphocyte count decreased (16.3%), aspartate aminotransferase increased (16.3%), hypertriglyceridaemia (15.0%), and rash (15.0%). Treatment interruption and permanent discontinuation due to TEAEs occurred in 6 (7.5%) patients each. Sixteen patients (20.0%) experienced SAEs. Four patients experienced TEAEs leading to death, all events are related to underlying disease or disease progression, none of which were related to LBL-007 or toripalimab. Out of 75 efficacy evaluable patients, ORR and DCR were 13.3% (10/75) and 48.0% (36/75), respectively. In 29 efficacy evaluable NPC patients, ORR and DCR were 20.7% (6/29), and 62.1% (18/29), respectively. Among the group of 12 anti-PD-(L)1 treatment-naïve NPC patients and 17 anti-PD-(L)1 treated NPC patients, the ORR were 33.3% (4/12) and 11.8% (2/17), DCR were 75.0% (9/12) and 52.9% (9/17), respectively; Of note, the mPFS was up to 11.9 months (95%CI: 1.3, not reached) in anti-PD-(L)1 treatment-naïve NPC patients. Conclusions: LBL-007 in combination with toripalimab is well tolerated in patients with advanced malignant tumors and has demonstrated encouraging preliminary efficacy in patients with advanced NPC with or without prior anti-PD-(L)1 therapy. Clinical trial information: NCT05102006. Citation Format: Yunpeng Yang, Yuanyuan Zhao, Wenfeng Fang, Yan Huang, Yaxiong Zhang, Yi Ba, Zhen Wang, Chao Deng, Desheng Hu, Wei Wang, Guiling Li, Suxia Luo, Zhichao Fu, Haisheng Zhu, Huili Wang, Shiwei Zhao, Tao Li, Charles Cai, Li Zhang. Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody toripalimab, in patients with advanced malignant tumors: A phase Ib/II, open-label, multicenter, dose escalation/expansion study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT227.