Vebreltinib Achieves Preliminary Responses in Non-CNS MET+ Solid Tumors

Further development of vebreltinib in patients with MET fusions is being considered following results from the phase 2 SPARTA trial.

Vebreltinib (Bozitinib) achieved lasting responses in a small cohort of patients with non–central nervous system (CNS) MET fusion solid tumors, according to a news release on findings from the phase 2 SPARTA trial (NCT03175224) from the drug’s developers, Apollomics Inc.¹

Topline data from the trial showed 6 confirmed responses across 14 patients with MET gene fusion solid tumors, yielding an overall response rate (ORR) of 43%. Specifically, a complete response occurred in 1 patient with third-line metastatic non–small cell lung cancer (NSCLC), and 5 partial responses occurred in those with NSCLC (n = 3), pancreatic cancer (n = 1), and intrahepatic bile duct cancer (n = 1).

Additionally, median overall survival (OS) and progression-free survival (PFS) were 12.4 months and 4.5 months, respectively. Furthermore, the median time to response was 3.7 months, and the median duration of response (DOR) was 5.6 months; 1 patient was continuing treatment after an 18-month DOR.

“We are very pleased with the preliminary data showing 43% [ORR] in patients with non-CNS MET fusion solid tumors. The results in this specific cohort of patients adds to the accumulating evidence supporting the potential of vebreltinib as a highly selective and efficacious treatment against multiple tumor types harboring MET alterations…The clinical evidence for the efficacy of vebreltinib in MET fusions is very encouraging,” Guo-Liang Yu, PhD, chairman, and chief executive officer of Apollomics, said in the news release.¹

The multi-cohort, single-arm open label phase 2 study included 14 patients with non-CNS MET fusion solid tumors as of the data cutoff date of July 31, 2024. Among patients with solid tumors, 6 had NSCLC, and 2 had intrahepatic bile duct cancer; there was 1 patient each with lung sarcomatoid cancer, colon cancer, pancreatic cancer, breast cancer, head and neck cancer, and esophageal cancer.

Most patients had at least 1 line of prior therapy except 2 patients with frontline disease. Patients received oral vebreltinib twice daily across treatment cohorts over 28-day cycles.² Patients with EGFR-positive NSCLC MET amplification received a standard-of-care EGFR inhibitor in addition to treatment with vebreltinib.

The primary end point of the study was ORR by independent review committee (IRC) assessment based on RECIST v1.1 criteria. Secondary end points included median DOR per IRC and investigator assessment; investigator-assessed ORR; clinical benefit rate (CBR) based on RECIST v1.1 guidelines; median time to progression; and PFS and OS at 6, 12, 18, and 24 months.

Key eligibility criteria included adult patients with non-CNS MET fusion solid tumors with the presence of at least 1 measurable lesion and an ECOG performance score from 0 to 1. Additionally, patients needed to have adequate organ function, a duration of 30 days or 5 half-lives since prior anticancer treatment—whichever was shorter—and a life expectancy of 3 months or greater from cycle 1 day 1, among other inclusion criteria.

Major exclusion criteria included hypersensitivity to vebreltinib; known actionable mutation/gene arrangements except EGFR-mutated NSCLC; active uncontrolled systemic bacterial, viral, or fungal infection or clinically significant, active disease process; or life-threatening illness, significant dysfunction of organ system, or comorbid conditions. Additional exclusion criteria included unstable angina or myocardial infarction within 1 year to treatment with vebreltinib, seropositive results consistent with active hepatitis C or hepatitis B infection, significant mental illness or substance abuse, the inability to swallow oral medication, and a history of another malignancy within 3 years prior to cycle 1 day 1.

References

1. Apollomics announces positive preliminary data of vebreltinib in patients with non-CNS MET fusion solid tumors from its phase 2 SPARTA trial. News release. Apollomics Inc. August 13, 2024. Accessed August 19, 2024. https://tinyurl.com/39xvjxjj
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 May 10, 2024. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT03175224