37P - Tislelizumab (TIS) combined with chemotherapy (CT) as first-line (1L) therapy for locally advanced or metastatic nonsquamous non-small cell lung cancer (LA/M nsq-NSCLC): Programmed death-ligand 1 (PD-L1) expression ≥50% subgroup analysis of the randomized, phase III RATIONALE-304 trial

Background

The open-label phase III RATIONALE-304 study (NCT03663205) compared the efficacy and safety of 1L TIS (a programmed cell death protein-1 inhibitor) plus CT (TIS+CT) vs CT in LA/M nsq-NSCLC. This analysis focused on patients (pts) from RATIONALE-304 with PD-L1 expression ≥50%.

Methods

Pts with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2:1) to 4–6 cycles of TIS + platinum-based CT and pemetrexed every 3 weeks (Q3W), followed by maintenance TIS and pemetrexed, or platinum-based CT and pemetrexed Q3W followed by maintenance pemetrexed. Progression-free survival (PFS) assessed by independent review committee (IRC) was the primary endpoint; secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety.

Results

The PD-L1 ≥50% population included 110 pts (TIS+CT, n=74; CT, n=36). At 16.5 months of median study follow-up (range 0.0–26.9 months), TIS+CT improved PFS compared with CT alone (stratified hazard ratio [HR]=0.31; 95% confidence interval [CI]: 0.18, 0.55), with median PFS (95% CI) of 14.6 months (11.5 months, not estimable [NE]) vs 4.6 months (3.5, 9.7 months), respectively. Median OS was NE for TIS+CT vs 13.1 months (HR=0.39; 95% CI: 0.22, 0.71) for CT. An ad hoc analysis at 23.4 months of median follow-up indicated median (95% CI) OS for TIS+CT of 43.4 months (24.2 months, NE) vs 13.1 months (5.6, 19.4 months) for CT (stratified HR=0.34; 95% CI: 0.21, 0.57). The confirmed ORR_IRC was 70.3% (95% CI: 58.5%, 80.3%) for TIS+CT and 30.6% (95% CI: 16.3%, 48.1%) for CT. Long-term exposure analysis (≥35 cycles) revealed a 4-year OS rate of 90.5% (95% CI: 67.0%, 97.5%), an ORR_IRC of 100%, and median DoR not reached (95% CI: 29.6 months, NE) for TIS+CT. The safety profile of TIS+CT was manageable and consistent with previous analyses.

Conclusions

In pts with LA/M nsq-NSCLC and PD-L1 expression ≥50%, 1L TIS+CT demonstrated clinically meaningful improvement in PFS, OS, ORR, and DoR, and a manageable safety profile compared with CT.

Clinical trial identification

NCT03663205.

Editorial acknowledgement

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

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

Y. Bao: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks/Shares: BeiGene. S. Lu: Financial Interests, Personal, Writing Engagements: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, BeiGene, Roche, Hansoh; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Hutchison, Roche, Simcere; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Personal, Advisory Board: Roche, Hengrui Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Member of Board of Directors: Innovent Biologics, INC. All other authors have declared no conflicts of interest.