1261P - Efficacy of glecirasib in combination with JAB-3312 as a front-line treatment for patients with KRAS p.G12C mutated NSCLC with PD-L1 expression levels or co-mutations

Background

The combination of glecirasib (KRAS G12C inhibitor) and JAB-3312 (SHP2 inhibitor) demonstrated a favorable safety profile and promising efficacy as a front-line treatment for non-small cell lung cancer (NSCLC) patients (pts) with KRAS G12C mutations, as presented at the ESMO 2023 and ASCO 2024. Here, we present the efficacy result of this combination in patients with varying levels of PD-L1 expression or co-mutations.

Methods

The phase 1/2a study [NCT05288205] evaluated multiple dose regimen combinations of glecirasib plus JAB-3312 in pts with KRAS p.G12C mutated solid tumors. Efficacy endpoints included objective response rate (ORR) and progression-free survival (PFS) by investigator per RECIST 1.1. Tumor cell proportion score (TPS) data of PD-L1 was collected either from local laboratory results or tested in central lab using baseline tumor samples. Co-mutations were also explored in this study.

Results

As of April 7^th, 2024, 102 pts with NSCLC received the combination therapy as a front-line treatment and were enrolled. The median follow-up duration was 10.1 months (range:1.2-20.9). The number of patients with PD-L1 TPS ≥50%, 1-49%, <1%, and unknown (lack of tumor tissues) was 14, 34, 41, and 13, respectively. The confirmed ORR was 64.7% (66/102), and in each PD-L1 subgroup, it was 71.4% (10/14), 73.5% (25/34), 63.4% (26/41), and 38.5% (5/13), respectively. The median PFS was not yet mature by the data cut-off date. The 6-month PFS rate was 70.7%, and in each PD-L1 subgroup, it was 64.6%, 76.3%, 72.3%, and 55.6%, respectively. The 12-month PFS rate was 52.4%, and in each PD-L1 subgroup, it was 64.6%, 49.5%, 63.4%, and 22.2%, respectively. Out of 55 pts with available baseline co-mutation data, co-alterations in SMARC family members were associated with a low ORR, while the most frequently co-mutated gene TP53 was not significantly associated with ORR.

Conclusions

Glecirasib plus JAB-3312 demonstrated a favorable ORR as a front-line treatment in KRAS p.G12C mutated NSCLC, regardless of PD-L1 expression. Co-mutations in SMARC family members may predict poor prognosis in this study population. More data will be presented at the incoming meeting.

Clinical trial identification

NCT05288205.

Editorial acknowledgement

Legal entity responsible for the study

Jacobio Pharmaceuticals.

Funding

Jacobio Pharmaceuticals.

Disclosure

All authors have declared no conflicts of interest.