December 2, 2022, Shanghai, China---Shanghai Haihe Biopharma Co., Ltd (referred as "Haihe Biopharma" or the “Company”), a company focusing on the discovery, development and commercialization of innovative anti-tumor drugs, announced that the latest results of its highly selective MET inhibitor SCC244 were presented at ESMO ASIA Congress 2022. The meeting is held in Singapore, during December 2 to 4, 2022.

Title：SCC244 plus Osimertinib in Patients with Stage IIIB/IIIC or IV, EGFR TKI resistant EGFR-mutant NSCLC Harboring MET Amplification
Report NO.: 607
Report Time: 2022-12-03 09:10-09:15
Presenter: Yongfeng Yu
Contents:
MET Amplification (METamp) commonly mediates resistance to EGFR Tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR mutation^1-3. 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^4-6. 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.^7,8 The open-label Phase Ib/II study (NCT: 04338243) was designed to evaluate the safety and efficacy of SCC244 combined with osimertinib in patients with locally advanced or metastatic EGFR-mutant NSCLC, which carries METamp and was resistant to EGFR TKI. 30 patients received combined treatment of SCC244 and Osimertinib. Overall, ORR was 60% [95% CI:40.6, 77.3], median DOR was 5.8 months [95% CI:3.9, 12.7], median PFS was 6.9 months [95% CI: 3.9, 8.9], and median OS was 16.9 months [95% CI:11.1, NE]. Among 19 patients with EGFR-mutant, T790M negative NSCLC who progressed on 1st or 2nd generation EGFR TKI, ORR was 73.7% [95% CI: 48.8, 90.9], median DOR was 6.2 months [95% CI: 3.3, NE], median PFS was 7.0 months [95% CI: 4.1, 13.8] and median OS was 15.1 months [95% CI:9.5, NE ]. The most common AE was Oedema (70.0%). The most common grade ≥3 treatment related adverse events (TRAE) were thrombocytopenia (16.7%) and neutropenia (16.7%). 6 patients discontinued due to TRAEs, none were solely attributed to SCC244. SCC244 plus osimertinib demonstrated clinical activity in EGFR-mutant NSCLC patients with METamp who are resistant to EGFR TKI. The safety profile was acceptable and manageable.

Title：A Pooled Analysis of MET TKI SCC244 in NSCLC Patients with MET Overexpression
Poster NO.:688
Contents:
The prevalence of MET overexpression in NSCLC patients varied from 5% to 75%⁹ and it may be concurrent with MET amplification. Several studies demonstrated that MET overexpression was an independent factor for poor prognosis among EGFR wild-type NSCLC patients and may be a potential therapeutic target in NSCLC patients^10-11.

The purpose of the study was to evaluate the efficacy of SCC244 in locally advanced or metastatic NSCLC patients with MET overexpression. The pooled analysis was performed on the efficacy data from two ongoing single-arm phase Ib studies (NCT03457532 and NCT04270591) of SCC244 in locally advanced or metastatic NSCLC patients. Only NSCLC patients with MET overexpression (IHC≥3+ as determined by central laboratory) not carrying METex14 skipping or EGFR mutation and with no EGFR-TKI inhibitor treatment were included in the analysis.

A total of 32 NSCLC patients were included in the analysis，including 12 treatment naïve patients who either refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ≥1 lines of prior systemic anti-tumor therapies. The result show that overall ORR was 37.5% (95% CI: 21.1, 56.3), 41.7% (95% CI: 15.2, 72.3) and 35.0% (95% CI: 15.4, 59.2) in treatment naïve and pre-treated patients, respectively. In the 32 patients, median DoR was 8.3 months (95% CI: 2.8, NE), median PFS was 6.9 months (95% CI: 3.6, 9.7), and median OS was 16.2 months (95% CI: 10.3, NE).

In this pooled analysis, SCC244 showed promising antitumor activity in patients with locally advanced or metastatic NSCLC with MET overexpression not carrying METex14 skipping or EGFR mutation. The preliminary efficacy result is favorable in comparison with standard chemotherapy in pre-treated patients. Further large-scale prospective studies are warranted to confirm these findings.