403O - Tislelizumab (TIS) plus chemotherapy (CT) vs placebo (PBO) plus CT as first-line (1L) treatment for recurrent or metastatic nasopharyngeal cancer (NPC): 3-year follow-up from the RATIONALE-309 study

Background

The RATIONALE-309 study met its primary endpoint at interim analysis, with 1L TIS + CT demonstrating statistically and clinically superior progression-free survival (PFS) compared to PBO + CT for patients (pts) with recurrent or metastatic NPC. Here we report longer follow-up results.

Methods

Treatment-naïve pts with recurrent or metastatic NPC were randomly assigned 1:1 to receive TIS 200 mg intravenously or PBO with gemcitabine + cisplatin every 3 weeks (Q3W) for 4-6 cycles, followed by TIS or PBO Q3W until disease progression (PD), unacceptable toxicity or withdrawal. After independent review committee (IRC)-confirmed PD, pts in the PBO arm could cross over to receive TIS alone. The primary endpoint was IRC-assessed PFS (PFS_IRC). Secondary endpoints included overall survival (OS), investigator-assessed PFS, time to second PD or death (PFS2) and safety. Efficacy analyses were done in the intent-to-treat population.

Results

263 pts were randomized (TIS + CT, n=131; PBO + CT, n=132). At data cutoff (Dec 8, 2023; median follow-up: 27.5 mo), sustained PFS_IRC improvement for TIS + CT was shown, with stratified HR (95% CI) of 0.53 (0.39, 0.71). Median PFS_IRC (95% CI) was 9.6 (7.6, 11.6) mo for TIS + CT and 7.4 (5.6, 7.6) mo for PBO + CT. TIS + CT demonstrated clinically meaningful OS improvement, with stratified HR of 0.73 (0.51, 1.05). Median OS (95% CI) was 45.3 (33.4, not estimable [NE]) mo for TIS + CT and 31.8 (25.0, NE) mo for PBO + CT. The impact of high in-study crossover (52.3%) on OS was assessed: stratified HR with the Rank-Preserving Structural Failure Time Model was 0.56 (0.27, 1.19) and with the two-stage method was 0.62 (0.40, 0.97) for TIS + CT vs PBO + CT. Median PFS2 (95% CI) was 45.3 (31.5, NE) mo for TIS + CT and 20.5 (13.9, 27.2) mo for PBO + CT; unstratified HR, 0.51 (0.34, 0.75). No unexpected safety signals were identified.

Conclusions

At 3-year follow-up in RATIONALE-309, TIS + CT continues to demonstrate sustained PFS benefit and clinically meaningful improvement in OS and PFS2 vs PBO + CT despite a high rate of crossover, with an acceptable safety profile, providing evidence for TIS as an effective 1L treatment option for pts with recurrent or metastatic NPC.

Clinical trial identification

NCT03924986.

Editorial acknowledgement

Medical writing support was provided by Izabela Bombik, PhD, of Parexel.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

Y. Wu, S. Yuan, C. Chen: Financial Interests, Personal, Stocks or ownership: BeiGene. S. Leaw: Financial Interests, Personal, Full or part-time Employment: Beigene Ltd. L. Zhang: Financial Interests, Personal, Invited Speaker: Sichuan Biokin Pharmaceutical, Akesobio; Financial Interests, Institutional, Research Grant, research grant & Trial Chair: AZ; Financial Interests, Institutional, Trial Chair: QiLu pharm, Henrui Pharm, Novartis, China Shiyao Pharma, Kelun Pharm, Sichuan Biokin Pharmaceutical, Pifzer, Pierre Fabre, Akesobio; Financial Interests, Institutional, Research Grant: Roche. All other authors have declared no conflicts of interest.