Abstract 1297P
Background
Primary results from the phase III RATIONALE-307 study (NCT03594747) showed efficacy and a manageable safety/tolerability profile for TIS, an anti-programmed cell death protein 1 monoclonal antibody, plus chemo, as 1L treatment for sq NSCLC. We report results based on smoking status.
Methods
Eligible pts (18–75 years) who were treatment-naïve for locally advanced or metastatic sq NSCLC were stratified by disease stage and programmed death-ligand 1 expression, and randomized 1:1:1 to Arm A: TIS 200 mg + paclitaxel (P) 175 mg/m2 and carboplatin (C) AUC 5 (every 3 weeks [Q3W], day [D] 1); Arm B: TIS + nab-paclitaxel 100 mg/m2 (Q3W, D 1, 8 and 15) + C (Q3W, D 1); or Arm C: P + C (Q3W, D 1). Chemo was administered for 4–6 cycles. Progression-free survival (PFS) by independent review committee (IRC), objective response rate (ORR) by IRC, and safety were assessed in pts who were smokers (former/current) and non-smokers.
Results
301 pts who were smokers with a median age of 62 years and 59 pts who were non-smokers with a median age of 58 years were randomized. Longer PFS and higher ORR were reported with TIS plus chemo vs chemo alone regardless of smoking status (Table). Treatment emergent adverse events (TEAEs) are summarized in the table.
Conclusions
Clinically meaningful improvements in PFS and ORR were observed with TIS plus chemo in pts with advanced sq NSCLC, irrespective of smoking status. The safety and efficacy profile of TIS plus chemo was consistent with the overall population of this phase III study. Table: 1297P
| Smokers | Non-smokers | |||||
| A (n=96) | B (n=107) | C (n=98) | A (n=24) | B (n=12) | C (n=23) | |
| n, (95% CI) | ||||||
| Median PFS, months | 7.6 (5.59, 10.41) | 7.6 (5.62, 9.86) | 5.5 (4.17, 5.78) | 7.5 (5.45, 7.82) | NE (4.17, NE) | 5.4 (2.79, 5.59) |
| Hazard ratio* | 0.534 (0.363, 0.786) | 0.556 (0.384, 0.803) | - | 0.475 (0.226, 1.000) | 0.119 (0.027, 0.533) | - |
| ORR, % | 75.0 (65.1, 83.3) | 73.8 (64.4, 81.9) | 50.0 (39.7, 60.3) | 62.5 (40.6, 81.2) | 83.3 (51.6, 97.9) | 47.8 (26.8, 69.4) |
| n=96 | n=106 | n=94 | n=24 | n=12 | n=23 | |
| n (%) | ||||||
| Pts with ≥ 1 TEAE | 96 (100.0) | 105 (99.1) | 94 (100.0) | 24 (100.0) | 12 (100.0) | 23 (100.0) |
| Grade ≥ 3 | 87 (90.6) | 91 (85.8) | 82 (87.2) | 19 (79.2) | 11 (91.7) | 16 (69.6) |
| Serious | 36 (37.5) | 42 (39.6) | 23 (24.5) | 8 (33.3) | 3 (25.0) | 6 (26.1) |
*Unstratified
Clinical trial identification
NCT03594747.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Tamsin Grewal, MSc, of Ashfield MedComms, an Ashfield Health Company, and funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
S. Lu: Financial Interests, Invited Speaker: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Speaker’s Bureau: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Research Grant: AstraZeneca, Hutchison, BMS, Hengrui Therapeutics, BeiGene, Roche, Hansoh; Non-Financial Interests, Principal Investigator: AstraZeneca, Hansoh; Financial Interests, Advisory Role: AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere, Zail Lab, GenomiCare, Yuan Corporation prIME Oncology, Menarini and Roche. C. Hu: Financial Interests, Speaker’s Bureau: AstraZeneca. S.J. Leaw: Financial Interests, Full or part-time Employment: BeiGene, Ltd. X. Lin: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd. J. Zhang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.