FDA Grants Orphan Drug Designation to Vebreltinib for NSCLC With MET Aberrations

The FDA has granted an orphan drug designation (ODD) to vebreltinib (APL-101) for the treatment of patients with non–small cell lung cancer (NSCLC) harboring MET genomic tumor aberrations.¹

Vebreltinib is a novel small molecule kinase inhibitor targeting c-MET, and it is a type 1b class highly selective c-MET inhibitor. The ongoing global phase 2 SPARTA trial (NCT03175224) is evaluating vebreltinib in patients with NSCLC and other solid tumors with MET genomic dysregulation.

“While NSCLC is the most common type of lung cancer, a subset of patients will have MET genomic dysregulations in their tumors which make them more resistant to treatment, presenting an unmet medical need,” Guo-Liang Yu, PhD, co-founder, chairman and chief executive officer of Apollomics, stated in a press release. “We are pleased to have received the ODD for vebreltinib, as patients need new and better treatment options. Through genomic testing, we can identify patients who will benefit most from a targeted treatment like vebreltinib.”

Preclinical studies have shown that vebreltinib demonstrated strong tumor inhibitory effects in c-MET dysregulated human gastric, hepatic, pancreatic and lung cancer xenograft animal models and patient-derived xenograft models.

Previously reported data from clinical trials showed that vebreltinib (PLB1001) displayed a generally well-tolerated safety profile and preliminary evidence of clinical activity in patients with NSCLC harboring a mutation that leads to MET exon 14 skipping and in patients with secondary glioblastoma multiforme harboring MET fusion and/or exon 14 skipping with evidence of brain penetration.

SPARTA is examining the efficacy of vebreltinib in patients with NSCLC with c-MET exon 14 skipping mutations, patients with cancers associated with c-MET amplifications, and patients with cancers associated with c-MET fusion.²

The trial is comprised of 7 cohorts:

• Cohort A-1: Previously untreated patients with NSCLC harboring a c-MET exon 14 skip mutation.
• Cohort A-2: Patients with NSCLC and a c-MET exon 14 skipping mutation who received 1 or 2 prior lines of treatment and are naïve to c-MET inhibitors.
• Cohort B: Patients with NSCLC and a c-MET exon 14 skipping mutation who received prior treatment and progressed on a prior c-MET inhibitor.
• Cohort C: Patients with tumor types except primary central nervous system (CNS) tumors with c-MET high-level amplifications.
• Cohort C-1: Patients with NSCLC harboring MET amplification and EGFR wild-type who are MET inhibitor naïve.
• Cohort D: Patients with tumor types except primary CNS tumors harboring c-MET fusions who are MET inhibitor naïve.
• Cohort E: Patients with primary CNS tumors with MET alterations who are MET inhibitor naïve.

Key exclusion criteria for all patients include hypersensitivity to vebreltinib, excipients of the drug product, or other components of the study treatment regimen; or known actionable mutation/gene rearrangement of EGFR (except for cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.

All patients in each cohort will receive 200 mg of oral vebreltinib twice daily. The primary end point of the trial is objective response rate per blinded independent review committee per RECIST v1.1 criteria. Secondary end points include duration of response, clinical benefit rate, time to progression, progression-free survival, overall survival, and safety.

References

1. 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 17, 2022. https://bit.ly/3TMuh46
2. 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 July 27, 2022. Accessed November 17, 2022. https://clinicaltrials.gov/ct2/show/NCT03175224