Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody tislelizumab with or without chemotherapy in patients with advanced nasopharyngeal cancer and other malignant tumors: A phase Ib/II dose escalation/expansion study.

6033 Background: Dual inhibition of PD-1 and LAG-3 is expected to synergistically increase immune response against tumor growth while chemotherapy can enhance the efficacy of immunotherapy through various mechanisms. Here we report the safety and efficacy of LBL-007 (anti-LAG-3) in combination with tislelizumab (anti-PD1) with or without chemotherapy in advanced solid tumors (Phase Ⅰb) and previously untreated patients with advanced nasopharyngeal carcinoma (NPC) (Phase II). Methods: In phase Ⅰb, patients with relapsed and refractory advanced solid tumor received LBL-007 (300 or 600 mg) plus tislelizumab (200 mg) (both i.v. Q3W), and in phase Ⅱ, patients with previously untreated recurrent or metastatic NPC patients received LBL-007 (600 mg) plus tislelizumab (200 mg) in combination with GC chemotherapy gemcitabine (1000 mg/m 2 ) and cisplatin (80mg/m 2 ) (i.v. Q3W). The primary endpoints were tolerability, safety, and efficacy. Results: Updated data with more follow up including duration of response and progression free survival will be available to report at the meeting. As of January 10, 2024, 21 patients (4 NPC, 7 NSCLC, 7 melanoma and 3 others) and 42 NPC patients were enrolled in in phase Ⅰb and phase Ⅱ respectively. The median follow-up was 13.1 months. During the study, no Dose limiting Toxicity (DLT) was observed, and Recommended Phase 2 Dose (RP2D) was determined to be 600mg Q3W for both chemo and chemo free regimens. In phase II, all grades TRAEs occurred in 39 patients (92.9%), with grade ≥3 TRAE in 24/42 patients (57.1%). The most common TRAEs (≥20%) included white blood cell count decreased, neutrophil count decreased, anaemia, ALT increased, AST increased, platelet count decreased, nausea, hyponatraemia, hypochloraemia, blood creatinine increased, vomiting, and hypothyroidism. Treatment interruption due to TEAEs occurred in 31 (73.8%) patients. 13 patients (31%) experienced SAEs. 1 patient experienced Grade 5 AE due to exacerbation of cachexia unrelated to LBL-007/tislelizumab. The clinical efficacy is shown in the table. Conclusions: LBL-007/tislelizumab combination is well-tolerated in patients with advanced malignant tumors. LBL-007/tislelizumab/GC combination showed manageable, no new safety concerns and encouraging antitumor activity in previously untreated and advanced NPC patients. The encouraging efficacy and safety profile may support a pivotal study with LBL-007 in combination with tislelizumab and GC chemotherapy for NPC development in 1L setting. Clinical trial information: NCT05516914 . Table: see text