Tagitanlimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC): Results from a randomized, double-blind, phase 3 study.

6004 Background: The addition of PD-1 inhibitor to gemcitabine and cisplatin (GP) showed promising activity as first-line therapy for R/M NPC. Here, we first report the PD-L1 inhibitor Tagitanlimab (KL-A167) plus GP compared with placebo plus GP in a randomized phase 3 study (KL167-Ⅲ-08, NCT05294172). Methods: Eligible patients (pts) with previously untreated R/M NPC were in 2:1 ratio randomly assigned to receive tagitanlimab or placebo (1200 mg, D1) in combination with cisplatin (80 mg/m 2 , D1) and gemcitabine (1000 mg/m 2 , D1 and D8) every 3 weeks (Q3W) for up to 6 cycles followed by tagitanlimab or placebo monotherapy Q3W until disease progression, unacceptable toxicity, or withdrawal of consent. After disease progression, pts from the placebo arm could crossover to receive tagitanlimab monotherapy. The primary endpoint was progression-free survival (PFS) assessed by the blinded independent central review (BICR) according to RECIST version 1.1. Results: Between Jun 16, 2022, and May 27, 2023, 295 pts were assigned to tagitanlimab plus GP arm (n = 197) or placebo plus GP arm (n = 98). The median age was 52 years, and 79.7% were male. As of Feb 4, 2024, 47.2% of pts in tagitanlimab plus GP arm vs 23.5% of pts in placebo plus GP arm were still on treatment, 36.7% of pts in placebo plus GP arm were crossed to receive tagitanlimab monotherapy after disease progression. The median follow-up time was 11.7 months. The PFS per BICR was met at the prespecified interim analysis with a 53% reduction in risk of progression or death (HR 0.47; 95% CI, 0.33 to 0.66; one-sided P <0.0001). The median PFS was not reached (95% CI, 10.9-NE) in tagitanlimab plus GP arm and 7.9 months (95% CI, 6.9-8.3) in placebo plus GP arm; the 12-month PFS rate was 56.7% vs 26.7%. The objective response rate (ORR) per BICR was 81.7% (95% CI, 75.6-86.9) in tagitanlimab plus GP arm and 74.5% (95% CI, 64.7-82.8) in placebo plus GP arm, with a median duration of response (DoR) of 11.7 months (95% CI, 8.2-NE) and 5.8 months (95% CI, 5.6-6.9; HR 0.48, 95% CI, 0.32-0.70), respectively. The overall survival (OS) benefit was observed in tagitanlimab plus GP arm vs placebo plus GP arm (median OS not reached for either arm; HR 0.62, 95% CI 0.32-1.22). The most common ≥ grade 3 treatment-related adverse events (tagitanlimab plus GP arm vs placebo plus GP arm) were neutrophil count decreased (57.9% vs 49.0%), white blood cell count decreased (52.8% vs 46.9%), and anemia (38.6% vs 40.8%). Conclusions: The addition of tagitanlimab to GP demonstrated superior PFS efficacy compared to GP alone, supporting that tagitanlimab, as a PD-L1 inhibitor, could be the new standard of treatment for pts with R/M NPC in the first-line setting. The safety profile of tagitanlimab combined with GP was manageable and consistent with previous reports, with no new safety signals identified. Clinical trial information: NCT05294172 .