Abstract 132P
Background
Interim analysis of the open-label phase 3 RATIONALE-307 study (NCT03594747) demonstrated clinical benefit, including significantly improved progression-free survival (PFS) with a manageable safety profile, of tislelizumab (TIS) plus chemotherapy (chemo) as first-line (1L) therapy in patients (pts) with advanced sq-NSCLC vs chemo alone. Here, we report updated results.
Methods
Adults with previously untreated stage IIIB (not amenable to curative surgery/radiotherapy)/IV sq-NSCLC were randomized (1:1:1) to intravenous TIS (200mg, 21-day cycles) + paclitaxel + carboplatin (Arm A); TIS + nab-paclitaxel + carboplatin (Arm B); or paclitaxel + carboplatin (Arm C). The primary endpoint was PFS in Arms A and B vs Arm C, per independent review committee (IRC). Secondary endpoints included overall survival, objective response rate (ORR), duration of response (DoR), and safety.
Results
As of 30 September 2020 (median follow-up 16.7 months), of 360 randomized pts, 355 received treatment. The updated median (95% confidence interval [CI]) PFS benefit was maintained for Arms A (7.7 [95%CI: 6.7, 10.4] months [mo], stratified hazard ratio [HR] 0.45 [95%CI: 0.33, 0.62]) and B (9.6 mo [95%CI: 7.4, 10.8], HR 0.43 [95%CI: 0.31, 0.60]) vs C (5.5 mo [95%CI: 4.2, 5.6]). Consistent improvements in ORR in Arms A (74.2% [95%CI: 65.4, 81.7]) and B (73.9% [95%CI: 65.1, 81.6]) vs C (47.9% [95%CI: 38.8, 57.2]) were observed. Median DoR in Arms A and B was 8.4 (95%CI: 5.0, 15.8) mo and 8.6 (95%CI: 7.1, 12.5) mo, respectively vs 4.3 (95%CI: 2.9, 5.4) mo in Arm C. The incidences of any grade (Arm A 100%; Arm B 99.2%; Arm C 100%) or ≥grade 3 (Arm A 89.2%; Arm B 87.3%; Arm C 84.6%) treatment-emergent adverse events (TEAE) were similar between arms. The rate of treatment discontinuation due to TEAE was similar between Arms A (17.5%) and C (15.4%), and lower than in Arm B (32.2%). No new safety signal was identified.
Conclusions
In RATIONALE-307, the addition of TIS to chemo continued to demonstrate clinical benefit as 1L treatment of advanced sq-NSCLC vs chemo alone after a longer follow-up, with a manageable safety profile.
Clinical trial identification
NCT03594747.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Arezou Hossein, MPharm, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
S. Lu: Financial Interests, Personal, Other, Research support: AstraZeneca, Hutchison, BMS, Heng Rui Beigene and Roche, Hansoh ; Financial Interests, Personal, Other, Speaker fees: AstraZeneca, Roche, Hansoh; Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Hutchison MediPharma, ZaiLab, GenomiCare, Novarti, Yuhan Corporation, Menarini., Mirati Therapeutics Inc, and Roche. C. Hu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. X. Lin, L. Liang, S. Leaw, W. Zheng: Financial Interests, Personal, Full or part-time Employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.