LBA6 - Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer: A multicentre, open-label, randomized phase III study

Background

Befotertinib (D-0316), a novel highly selective oral third-generation EGFR-TKI, exhibited encouraging antitumor activity in a pivotal phase II study (NCT03861156) in EGFR T790M mutation-positive patients (pts). This phase III, open-label, randomized trial was conducted to compare the efficacy and safety of befotertinib versus icotinib as first-line treatment in pts with previously untreated, locally advanced or metastatic NSCLC with EGFR-sensitizing mutation (Del19 or L858R).

Methods

Eligible stage IIIB/IIIC/IV NSCLC pts with confirmed EGFR Del19 or L858R mutation were randomly assigned (1:1) to receive either befotertinib (75–100 mg once daily) or icotinib (125 mg thrice daily) as first-line therapy. The primary endpoint was progression free survival (PFS) assessed by independent central review (IRC). Second endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) by IRC, and safety.

Results

Between Dec 24, 2019 and Dec 28, 2020, 362 pts were randomized to receive befotertinib (n=182) and icotinib (n=180). At a median follow-up of 20.6 months, median PFS by IRC was 22.1 months for befotertinib and 13.8 months for icotinib (HR 0.49 [95% CI 0.36-0.68]; p<0.0001). ORR was 75.8% and 78.3%, DCR was 94.5% and 98.3% for befotertinib and icotinib arms, respectively. Median DOR was 12.4 months for icotinib arm but not reached for befotertinib arm. OS data were immature in both treatment arms. Median treatment duration was 16.4 months with befotertinib versus 11.1 months with icotinib. Grade≥3 treatment-emergent adverse events (TEAEs) were observed in 86 pts (47.3%) for befotertinib arm and in 54 (30.0%) for icotinib arm. Drug-related deaths occurred in 2 (1.1%) versus 1 (0.6%) pts in the befotertinib versus icotinib arm.

Conclusions

Befotertinib demonstrated superior efficacy compared with icotinib in the first-line treatment for advance pts with EGFR mutation-positive NSCLC, with an acceptable safety profile.

Clinical trial identification

NCT04206072.

Editorial acknowledgement

Editorial assistance in the writing of the abstract that was provided by Betta Pharmaceuticals Co., Ltd., Hangzhou, China.

Legal entity responsible for the study

Betta Pharmaceuticals Co., Ltd., Hangzhou, China.

Funding

Betta Pharmaceuticals Co., Ltd., Hangzhou, China.

Disclosure

S. Lu: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Hansoh, Hengrui, Roche; Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer lngelheim, GenomiCare, Hutchison MediPharma, InventisBio Co.Ltd, Menarini, Prizer, Roche, Yuhan Corporation, ZaiLab; Non-Financial Interests, Personal, Research Grant: AstraZeneca, BeiGene, BMS, Hansoh, Hengrui, Hutchison, Lilly Suzhou Pharmaceutical Co., Ltd., Roche. L. Ding: Financial Interests, Personal, Stocks/Shares: Betta Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.