Abstract 1290P
Background
Primary results from the phase III RATIONALE-304 study (NCT03663205) 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 advanced or metastatic non-sq NSCLC. Here, we report results based on smoking status.
Methods
Eligible pts (aged 18–75 years) who were treatment-naïve for locally advanced or metastatic non-sq NSCLC were stratified by disease stage and programmed death-ligand 1 expression, and randomized 2:1 to receive TIS (200 mg intravenously [IV]) plus platinum (carboplatin AUC 5 or cisplatin 75 mg/m2 IV) + pemetrexed 500 mg/m2 (PP) every three weeks followed by maintenance TIS + pemetrexed (Arm A), or PP followed by maintenance pemetrexed (Arm B). 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
213 pts who were smokers with a median age of 61 years and 121 pts who were non-smokers with a median age of 59 years were randomized. PFS was longer with TIS plus chemo vs chemo alone for pts who were smokers (Table). ORR was higher with TIS plus chemo vs chemo alone for both smokers and non-smokers. Treatment emergent adverse events (TEAEs) occurring in smokers and non-smokers are summarized in the table.
Conclusions
Clinically meaningful improvements in PFS were observed with TIS plus chemo in pts with advanced non-sq NSCLC who were smokers. The safety and efficacy profile of TIS was consistent with the overall population of this phase III study. Table: 1290P
| Smokers | Non-smokers | |||
| Arm A (n=147) | Arm B (n=66) | Arm A (n=76) | Arm B (n=45) | |
| n, (95% CI) | ||||
| Median PFS, months | 9.7 (7.72, 11.53) | 4.6 (4.11, 7.62) | 8.5 (5.75, 11.86) | 7.7 (5.82, 11.73) |
| Hazard ratio* | 0.466 (0.311, 0.697) | - | 1.075 (0.596, 1.940) | - |
| ORR, % | 61.2 (52.8, 69.1) | 31.8 (20.9, 44.4) | 50.0 (38.3, 61.7) | 44.4 (29.6, 60.0) |
| n=146 | n=66 | n=76 | n=44 | |
| n (%) | ||||
| Grade ≥ 3 TEAEs | 99 (67.8) | 36 (54.5) | 51 (67.1) | 23 (52.3) |
| Serious TEAEs | 52 (35.6) | 15 (22.7) | 22 (28.9) | 8 (18.2) |
| Immune-related TEAEs | 38 (26.0) | NA | 19 (25.0) | NA |
*Unstratified
Clinical trial identification
NCT03663205.
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; 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, Roche. Y. Bao: Financial Interests, Full or part-time Employment: BeiGene, Ltd. L. Liang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. X. Qiu: Financial Interests, Full or part-time Employment: BeiGene, Ltd. L. Zhang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.