622P - Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in solid tumors with KRAS G12C mutation: Results from a phase Ib/II study

Background

Ifebemtinib is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). D-1553 (garsorasib) is a novel oral and potent KRAS G12C inhibitor. KRAS G12Ci’s overall response rate (ORR) was 9-29% in previously-treated KRAS G12C mutant colorectal cancer (CRC) with D-1553’s ORR as 20.8%. Preclinical data showed that ifebemtinib combined with KRAS G12Ci had synergistic anticancer effect in multiple KRAS G12C mutant cancer models. This study is to evaluate clinical safety and antitumor activity of ifebemtinib combined with D-1553 in KRAS G12C mutant solid tumors. Here we report data from phase II of first-line non-small cell lung cancer (NSCLC) and second-line or beyond CRC with KRAS G12C mutation.

Methods

Locally advanced or metastatic NSCLC patient (pts) without prior systemic anticancer therapy and metastatic CRC pts with at least 1 prior line of anticancer therapy were enrolled and received ifebemtinib (100mg qd) + D-1553 (600mg bid). KRAS G12C mutation status was identified in tumor tissues.

Results

As of 15 April 2024, 33 KRAS G12C mutant NSCLCs (81.8% stage IV) and 15 KRAS G12C mutant metastatic CRCs were enrolled and received ifebemtinib + D-1553 treatment. Median follow-up (FU) time were 4.6m (range: 1.1-11.7) in NSCLC cohort and 5.7m (range: 2.1-12.3) in CRC cohort. In NSCLC cohort, ORR was 83.9% (95%CI: 66.3, 94.6), disease control rate (DCR) was 96.8% (95%CI: 83.3, 99.9), median progression-free survival (mPFS) and overall survival (OS) were not reached. In CRC cohort, ORR was 50.0% (95%CI: 23.0, 77.0), DCR was 85.7% (95%CI: 57.2, 98.2), mPFS was 7.7m (95%CI: 2.8, NE), mOS was not reached. The safety profile of ifebemtinib + D-1553 both in NSCLCs and CRCs is comparable to each single agent without adding toxicities. No ifebemtinib- or D-1553-related Grade 4/5 AEs were reported. 7 pts (14.6%) had ifebemtinib-related SAEs, and 6 (12.5%) were also considered D-1553 related. 10 pts (20.8%) had Grade 3 ifebemtinib-related AEs, and all were also D-1553 related.

Conclusions

The combination of ifebemtinib and D-1553, as a dual-oral regimen, showed promising antitumor activity and manageable safety profile in KRAS G12C mutant solid tumors. Long term FU is needed to assess the potential of such novel combo.

Clinical trial identification

NCT06166836; NCT05379946.

Editorial acknowledgement

Legal entity responsible for the study

InxMed (Shanghai) Co., Ltd, shanghai, China.

Funding

InxMed (Shanghai) Co., Ltd, shanghai, China.

Disclosure

All authors have declared no conflicts of interest.