Updated efficacy, safety and biomarker analysis of a phase 2 study of LBL-007 (alcestobart, an anti-LAG-3 mAb) combined with tislelizumab (an anti–PD-1 mAb) and chemotherapy in previously untreated recurrent or metastatic nasopharyngeal carcinoma (R/M NPC).

Abstract

6097 Background: For the first time weevaluated LBL-007 in combination with tislelizumab and chemotherapy in previously untreated R/M NPC in a prospective, multi-center phase 2 study. Preliminary findings indicated this combination had encouraging ORR in this patient population (2024 ASCO, abstr 6033). Here we present the updated efficacy, safety and biomarker analysis of this study focusing on previously untreated R/M NPC (NCT05516914). Methods: Untreated R/M NPC patients received gemcitabine at 1 g/m² on days 1 and 8, cisplatin at 80 mg/m² on day 1 (GP) in combination with LBL-007 600 mg and tislelizumab 200 mg on day 1 of every 3 weeks, the chemotherapy was up to 6 cycles, followed by LBL-007 and tislelizumab on day 1 of every 3 weeks as maintenance therapy. The primary endpoint was efficacy, and the secondary endpoints included safety and biomarker analysis. Results: As of January 13, 2025, 42 patients with NPC were enrolled and received LBL-007 in combination with tislelizumab plus chemotherapy as first-line treatment. The median follow-up was 17.1 months. Out of 41 efficacy evaluable patients, the ORR and DCR were 85.4% and 100%, the mPFS was 15.0 months and the mDoR was 14.7 months. mOS is not mature. A favorable trend of improved efficacy with LBL-007 combined with tislelizumab plus chemotherapy was observed compared to tislelizumab plus chemotherapy (mPFS 9.6 months, mDoR 8.5 months; NCT03924986). All-grade TRAEs occurred in 39 patients (92.9%), with grade ≥3 TRAEs in 29/42 patients (69.0%). Treatment permanent discontinuance due to LBL-007 TRAEs occurred in 2 (4.8%) patients. 16 patients (38.1%) experienced LBL-007 treatment related SAEs. TRAEs leading to death occurred in 1 patient and infusion-related reaction happened in 4 patients. No new safety signal was observed. Patients with LAG-3 expression ≥5% potentially had improved efficacy compared to those with <5% (Table 1). Conclusions: LBL-007/tislelizumab combined with GP chemotherapy has shown encouraging ORR, PFS and DoR in R/M NPC as first-line treatment with favorable safety profiles. These findings support a pivotal phase III study comparing LBL-007/tislelizumab plus GP with tislelizumab plus GP in R/M NPC in 1L setting. The correlation between higher LAG-3 expression and improved efficacy was observed, which warranted further validation in larger population. Clinical trial information: NCT05516914 . Clinical outcomes of efficacy evaluable patients. LAG-3＜5%N=10 a LAG-3≥5%N=27 a TotalN=41 ORR, N(%) 7 (70%) 25 (92.6%) 35 (85.4%) DCR, N(%) 10 (100%) 27 (100%) 41 (100%) mPFS (95%CI), months 12.1 (3.3, NE) 15.8 (9.7, NE) 15.0 (9.7, NE) mDoR (95%CI), months 8.8 (3.2, NE) 14.7 (8.3, NE) 14.7 (8.6, NE) 15-month PFS rate, % (95%CI) 40.0% (12.3%, 67.0%) 53.9% (33.4%, 70.7%) 49.8% (33.6%, 64.1%) a LAG-3 was evaluated in 37 patients.