106P - Efficacy and safety of IBI351 (GFH925) monotherapy in metastatic colorectal cancer harboring KRASG12C mutation: Updated results from a pooled analysis of two phase I studies

Background

IBI351 (GFH925) is an irreversibly covalent inhibitor of KRAS^G12C. Previously, a pooled analysis of two phase I studies reported preliminary efficacy and safety of IBI351 (GFH925) monotherapy in metastatic colorectal cancer (CRC) harboring KRAS^G12C mutation (Ying Yuan, et al., ASCO 2023). Herein, we present updated results of these two studies with extended follow-up.

Methods

The studies enrolled eligible metastatic CRC patients (pts) with KRAS^G12C. Pts received IBI351 (GFH925) orally at dose levels of 700mg once daily (QD) or 450/600/750mg twice daily (BID). The primary endpoint was objective response rate (ORR) assessed by investigator per RECIST v1.1.

Results

As of June 13, 2023, a total of 56 pts were enrolled (median age: 58.0 years; male: 60.7%; ECOG PS 1: 73.2%; ≥2 prior lines of treatment: 60.7%; liver metastasis: 60.7%). The median treatment duration was 172.5 days (range: 8-481) and 26 pts (46.4%) were still on treatment. For 48 pts at 600mg BID, confirmed ORR was 45.8% (95%CI: 31.4%-60.8%) and disease control rate (DCR) was 89.6% (95%CI: 77.3%-96.5%). Median duration of response (DOR) was not reached with events occurring in 5 (22.7%) pts. DOR rates were 65.5% (95%CI: 34.4%-84.5%) at 6 months and not reached at 9 months. In pts of all dose levels, treatment-related adverse events (TRAEs) occurred in 53 (94.6%) pts while majority of them were grade 1-2. Grade 3 TRAEs occurred in 13 (23.2%) pts. Neither grade 4-5 TRAEs nor treatment-related serious adverse events (TRSAEs) occurred. The most common TRAEs included anemia (48.2%), white blood cell count decreased (30.4%), blood bilirubin increased (26.8%) and pruritus (26.8%). TRAEs leading to dose reduction and interruption occurred in 6 (10.7%) and 12 (21.4%) pts. No TRAEs leading to treatment discontinuation or death occurred.

Conclusions

The updated results of IBI351 (GFH925) monotherapy showed promising durable efficacy and manageable safety in metastatic CRC harboring KRAS^G12C mutation. During longer follow-up, these two ongoing studies are expected to provide more robust evidence.

Clinical trial identification

NCT05005234; NCT05497336.

Editorial acknowledgement

Corresponding author: Kefeng Ding.

Legal entity responsible for the study

Innovent Biologics, Inc., Suzhou, Jiangsu, China.

Funding

Innovent Biologics, Inc., Suzhou, Jiangsu, China.

Disclosure

All authors have declared no conflicts of interest.