305MO - SCC244 plus osimertinib in patients with stage IIIB/IIIC or IV, EGFR TKI resistant EGFR-mutant NSCLC harboring MET amplification

Background

MET Amplification (METamp) commonly mediates resistance to EGFR TKIs in NSCLC patients with EGFR-mutation. Several clinical trials showed that the combination of MET inhibition with EGFR TKI is a promising therapeutic strategy to overcome the MET amplification-mediated resistance. SCC244 is a highly selective small molecular inhibitor of MET kinase. It was well tolerated and has shown favorable anti-tumor activities in patients with MET aberration as monotherapy in clinical studies.

Methods

This is an open-label Phase Ib/II study (NCT: 04338243) to evaluate the safety and efficacy of SCC244 combined with Osimertinib in pts with locally advanced or metastatic EGFR-mut NSCLC, which carries METamp and was resistant to EGFR TKI. 30 pts received combined treatment of SCC244 at 200mg QD or 300mg QD, and Osimertinib at a fixed dose of 80mg QD until disease progression or intolerable toxicity in Phase Ib. Tumor response was assessed every 6 weeks. The primary endpoint for Phase Ib was ORR (RSCIST v1.1) by investigator.

Results

Overall, ORR was 60% [95% CI:40.6, 77.3], mDOR was 5.8 months [95% CI:3.9, 12.7 ], mPFS was 6.9 months [95% CI: 3.9, 8.9] and mOS was 16.9 months [95% CI:11.1, NE ]. Among 19 pts with EGFR-mut, T790M negative NSCLC who progressed on 1^st or 2^nd generation EGFR TKI, ORR was 73.7%[95% CI: 48.8, 90.9], mDOR was 6.2 months [95% CI: 3.3, NE], mPFS was 7.0 months [95% CI: 4.1, 13.8] and mOS was 15.1 months [95% CI:9.5, NE ]. In 30 pts, the most common AE was Oedema (70.0%). The most common grade ≥3 TRAEs were Thrombocytopenia (16.7%) and Neutropenia (16.7%). 6 pts discontinued due to TRAEs, none were solely attributed to SCC244.

Conclusions

SCC244 plus Osimertinib demonstrated clinical activity in EGFR-mutant NSCLC pts with METamp and resistant to EGFR TKI. The safety profile was acceptable and manageable.

Clinical trial identification

NCT: 04338243.

Editorial acknowledgement

Legal entity responsible for the study

Haihe Biopharma Co., Ltd.

Funding

Haihe Biopharma Co., Ltd.

Disclosure

M. Sun, J. Zhang, M. Li, Y. Ren: Other, Institutional, Full or part-time Employment: Haihe Biopharma Co., Ltd. All other authors have declared no conflicts of interest.