LBA12 - Efficacy and safety of IBI351 (GFH925), a selective KRASG12C inhibitor, monotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Initial results from a registrational phase II study

Background

IBI351 is a covalent and irreversible inhibitor of KRAS^G12C. In a first-in-human phase I study (Zhou et al. Cancer Res 2023; 83: CT030), IBI351 showed promising efficacy in advanced NSCLC pts harboring KRAS^G12C. Here, we report results of IBI351 monotherapy for advanced NSCLC in an open-label, single-arm phase II pivotal study.

Methods

Eligible NSCLC pts harboring KRAS^G12C who failed standard therapy were enrolled. IBI351 600 mg was orally administered twice daily. Primary endpoint was confirmed objective response rate (ORR) assessed by independent radiological review committee (IRRC) as per RECIST v1.1. Other endpoints were safety, IRRC confirmed disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS) and overall survival (OS).

Results

As of June 13, 2023, 116 pts were enrolled (median age: 63.0 years; males: 87.9%; ECOG PS 1: 91.4%; ≥2 prior lines of treatment: 41.4%; stage IV: 96.6%; brain metastasis: 30.2%). Median treatment duration was 188 days (range: 11-342) with 43 (37.1%) pts remaining on treatment. Unconfirmed ORR was 59.5% (95%CI: 50.0-68.5) and confirmed ORR was 46.6% (95%CI: 37.2-56.0) which reached pre-specified endpoint. DCR was 90.5% (95%CI: 83.7-95.2). Median DoR was 8.3 months (95%CI: 6.3-NC) with events occurring in 17 (31.5%) pts. 29 (53.7%) pts with confirmed response still on treatment. Median TTR was 1.4 months (range: 1.2-6.9). With a median follow-up of 8.2 months (95%CI: 7.0-8.3), median PFS was 8.3 months (95%CI: 5.6-10.4). Median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 105 (90.5%) pts while 47 (40.5%) pts had grade≥3 TRAEs. Common TRAEs were anemia (42.2%), alanine aminotransferase increased (27.6%), aspartate aminotransferase increased (27.6%), asthenia (26.7%) and protein urine present (25.0%). Serious TRAEs occurred in 26 (22.4%) pts. TRAEs leading to treatment discontinuation occurred in 8 (6.9%) pts.

Conclusions

IBI351 continues to demonstrate encouraging efficacy with manageable safety. These results support IBI351 monotherapy as a potential new treatment option for advanced KRAS^G12C mutant NSCLC pts.

Clinical trial identification

NCT05005234.

Editorial acknowledgement

Yi-Long Wu.

Legal entity responsible for the study

Innovent Biologics, Inc., Suzhou, China.

Funding

Innovent Biologics, Inc., Suzhou, China.

Disclosure

J. Huang, M. Huang, Y. Shen: Financial Interests, Personal, Other, employee: Innovent Biologics, Inc. All other authors have declared no conflicts of interest.