LBA9 - Final overall survival (OS) results of befotertinib in patients with pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)

Background

Befotertinib (D-0316), a novel third-generation EGFR-TKI, showed a favorable progression-free survival (PFS) benefit and manageable in pretreated patients (pts) with EGFR T790M-positive NSCLC.

Methods

Adult pts received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily until disease progression or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee; secondary endpoints included investigator-assessed ORR, disease control rate (DCR), PFS, duration of response (DOR), intracranial PFS (iPFS), iORR, OS and safety. Herein, we present the investigator-assessed final OS, PFS, ORR, iORR, iPFS and safety data.

Results

At data cutoff (May 31, 2023), 133 (76%) deaths occurred in cohort A while 161 (56%) death in cohort B. The median duration of follow-up for OS was 47.9 months (95% CI: 47.1–48.3) in cohort A and 36.7 months (35.9–37.9) in cohort B. The median OS was 23.9 months (95% CI: 21.1–27.2) in cohort A and 31.5 months (26.8–35.3) in cohort B. The ORR was 54.5% (95% CI 46.9%–62.1%) in the cohort A and 66.2% (95% CI 60.4%–71.6%) in the cohort B. The median PFS was 11.0 months (95% CI 9.6–12.5) in the cohort A and 12.5 months (11.1–14.0) in the cohort B. The median DOR was 12.5 months and 13.6 months, DCR was 93.2% and 94.8%, iPFS was 16.5 (95% CI 8.6–NE) and 34.5 months (13.8–NE), iORR was 26.7% and 57.1% for cohort A and cohort B, respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1% in the cohort A and 50.3% in the cohort B, in which 22.2% and 31.7% were related to the study drug.

Conclusions

Befotertinib exhibited notable efficacy in both dose cohorts, showing a comparable OS benefit with other 3^rd-generation EGFR TKIs in cohort A (50 mg), while even greater OS benefits in cohort B. Further, safety remained manageable and consistent with prior assessments. Overall, befotertinib maintained its remarkable efficacy with a manageable safety profile in pretreated pts with confirmed T790M mutation-positive NSCLC.

Clinical trial identification

NCT03861156.

Editorial acknowledgement

Legal entity responsible for the study

Betta Pharmaceuticals Co., Ltd.

Funding

Betta Pharmaceuticals Co., Ltd.

Disclosure

S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AstraZeneca, Prizer, Boehringer Ingelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co. Ltd., Roche, Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co. Ltd.; Financial Interests, Personal, Coordinating PI: FibroGen. All other authors have declared no conflicts of interest.