LBA58 - Pathological response to neoadjuvant tislelizumab (TIS) plus platinum-doublet (PtDb) chemotherapy (CT) in resectable stage II-IIIA NSCLC patients (pts) in the phase III (Ph3) RATIONALE-315 trial

Background

Neoadjuvant (NA) CT with anti-PD-(L)1 mAb has shown promising pathologic response rates (ie, major pathological response [MPR], pathological complete response [pCR]) in pts with resectable NSCLC. The Ph3 RATIONALE-315 study (NCT04379635) investigated the efficacy & safety of NA TIS (anti-PD-1 mAb) or placebo (PBO) + CT, then adj TIS or PBO, in pts with resectable stage II-IIIA NSCLC.

Methods

This study enrolled pts with treatment (tx)-naïve, resectable, confirmed squamous (sq) or non-sq (nsq) stage II-IIIA NSCLC who were eligible for PtDb CT, with ECOG PS ≤1 and no known EGFR mutation (nsq) or ALK gene translocation (sq & nsq). Pts stratified by histology, disease stage, and PD-L1 expression (≥1% vs <1%) were randomized (1:1) to 3-4 cycles of TIS 200 mg IV Q3W or PBO, plus PtDb CT, followed by surgery + 8 cycles of adj TIS 400 mg IV Q6W or PBO. Primary endpoints: MPR rate after completion of NA tx + EFS per RECIST v1.1 by blinded independent review committee (IRC). Key secondary endpoint: pCR rate.

Results

As of 20 Feb 2023 (median follow-up: 16.8 mo), 453 pts (TIS + CT, n=226; CT, n=227) were randomized to the intention-to-treat (ITT) population and had similar baseline characteristics. Of 452 (99.8%; n=226 both arms) pts treated in the NA phase, 421 (92.9%) completed NA tx (TIS + CT, n=211 [93.4%]; CT, n=210 [92.5%]); 90 (19.9%) did not undergo surgery (TIS + CT, n=36 [15.9%]; CT, n=54 [23.8%]). Efficacy & safety data from the NA phase are summarized in the table; MPR & pCR rates were significantly improved with TIS + CT vs CT (P<0.0001). TIS + CT did not impact the feasibility of surgery. Table: LBA58

Efficacy and safety summary

^aAssessed by IRC.^b1-sided.^cRandomized pts who received ≥1 dose of any study drug.OR, odds ratio; TEAE, treatment-emergent adverse event.

Conclusions

TIS + CT showed clinically meaningful and statistically significant improvements in MPR and pCR rates vs PBO + CT as NA tx. The safety profile of TIS + CT was consistent with known risks of each tx and was manageable in pts with resectable stage II-IIIA NSCLC, further supporting this tx combination for these pts.

Clinical trial identification

NCT04379635.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Apurva Davé, PhD, of Medical Expressions, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

J. Zhang: Financial Interests, Personal, Full or part-time Employment: BeiGene Ltd. All other authors have declared no conflicts of interest.