Vebreltinib Receives Approval in China For MET Exon 14+ NSCLC

China’s National Medical Products Administration (NMPA) has granted conditional marketing approval to vebreltinib (APL-101; PBL-1001) for the treatment of patients with non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations.¹

The highly selective, potent, c-Met inhibitor is an orally bioavailable small molecule, which inhibits the abnormal activation of the HGF/c-Met axis–a pathway involved in tumor growth, proliferation, and the emergence of resistance to certain targeted therapies. By targeting c-Met, vebreltinib represents a potential therapy for patients within this population, as well as patients with other cancers characterized by MET alterations.

"The NMPA approval of vebreltinib is an important milestone toward providing a new treatment option for patients with MET exon 14–skipping NSCLC in China. Apollomics extends its full support and congratulations to Avistone on this significant achievement," Guo-Liang Yu, PhD, chairman and chief executive officer of Apollomics, stated in a news release.¹

Data from the phase 2 KUNPENG trial (NCT04258033) presented at the 2023 ESMO Congress showed that vebreltinib elicited an objective response rate (ORR) of 75.0% (95% I, 61.1%-86.0%) in all evaluable patients (n = 52) per blinded independent central review (BICR). All responders achieved a partial response, and the rates of stable disease and progressive disease were 21.2% and 1.9%, respectively. In patients who were treatment naive (n = 35) and previously treated (n = 17), the ORRs were 77.1% (95% CI, 59.9%-89.6%) and 70.6% (95% CI, 44.0%-89.7%), respectively.²

The study enrolled patients at least 18 years of age with stage IIIB or IV NSCLC harboring MET exon 14 skipping mutations who had an ECOG performance status of 0 or 1.

Patients received 200 mg of vebreltinib twice per day during 28-day cycles. BICR-assessed ORR per RECIST v1.1 criteria served as the trial’s primary end point. Secondary end points included investigator-assessed ORR, disease control rate, duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety.

Additional data for the overall cohort showed that per BICR assessment, the median DOR was 15.9 months (95% CI, 9.2-17.8), and the median TTR was 1.0 months (95% CI, 1.0-2.6). The median PFS was 14.1 months (95% CI, 6.4-17.9), and the 6- and 12-month PFS rates were 71.2% (95% CI, 56.8%-81.5%) and 53.7% (95% CI, 39.3%-66.1%), respectively. The median OS was 20.7 months (95% CI, 16.2–not evaluable).

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 77.0% of all evaluable patients (n = 113), and the rate of grade 3 or higher TRAEs was 31.0%. The most common TRAEs were peripheral edema (56.6%), hypoalbuminemia (22.1%), and hypoproteinemia (19.5%).

The ongoing, multi-cohort, phase 2 study SPARTA trial (NCT03175224) is investigating the efficacy and safety of vebreltinib at over 90 centers in 13 countries in patients with MET exon 14 skipping–positive NSCLC.¹ Cohort A-1 is currently recruiting patients in the first-line setting, cohort A-2 is recruiting patients who were previously treated with less than 3 lines of therapy and were naive to a MET inhibitor. Cohort B is including patients who have received at least 3 prior lines of therapy. Additionally, Cohort C will evaluate histology agnostic MET amplified cancers, though this will exclude primary central nervous system tumors.³

All patients must be at least 18 years of age to enroll on the study. Key inclusion criteria included the presence of at least 1 measurable targetable lesion; an ECOG performance status of 0 or 1; acceptable organ and cardiac function; and a life expectancy of at least 3 months. Exclusion criteria known actionable mutations or gene arrangements including ALK, ROS1, RET, NTRK, KRAS, and BRAF (excluding applicable cohorts); and unstable angina or myocardial infarction within 1 year prior to initiation of study treatment.

All patients are receiving vebreltinib monotherapy. ORR is serving as the trial’s primary end point, and secondary end points include DOR, clinical benefit rate, time to progression, and PFS.

In November of 2022, the FDA granted an orphan drug designation to vebreltinib for the treatment of patients within this population.⁴

"Our collaboration with Avistone and our ongoing global SPARTA trial with vebreltinib underscores our dedication to developing novel therapies for difficult to treat cancers and drug resistant patients worldwide,” Yu concluded.¹

References

1. Apollomics announces the first approval of vebreltinib for MET exon 14 skip non-small cell lung cancer. News release. Apollomics Inc. November 16, 2023. Accessed November 16, 2023. https://ir.apollomicsinc.com/news-releases/news-release-details/apollomics-announces-first-approval-vebreltinib-met-exon-14-skip
2. Yang J-J, Zhang Y, Wu L, et al. Preliminary results of phase II KUNPENG study of vebreltinib in patients (Pts) with advanced NSCLC harboring c-MET alterations. Ann Oncol. 2023;34(suppl 2):S791. doi:10.1016/j.annonc.2023.09.2412
3. APL-101 study of subjects with NSCLC with c-MET exon 14 skip mutations and c-MET dysregulation advanced solid tumors (SPARTA). ClinicalTrials.gov. Updated October 23, 2023. Accessed November 16, 2023. https://clinicaltrials.gov/ct2/show/NCT03175224
4. Apollomics Inc. receives FDA orphan drug designation for vebreltinib (APL-101) for treatment of non-small cell lung cancer with MET genomic tumor aberrations. News release. Apollomics Inc. November 15, 2022. Accessed November 16, 2023. https://www.globenewswire.com/news-release/2022/11/15/2556092/0/en/Apollomics-Inc-Receives-FDA-Orphan-Drug-Designation-for-Vebreltinib-APL-101-for-Treatment-of-Non-Small-Cell-Lung-Cancer-with-MET-Genomic-Tumor-Aberrations.html