Vebreltinib Induces Responses in non-CNS MET Fusion+ Solid Tumors

The orally bioavailable and highly selective c-MET inhibitor, vebreltinib (APL-101), elicited an objective response rate (ORR) of 43% in a cohort of patients with non–central nervous system (CNS) solid tumors harboring MET fusions enrolled in the phase 2 SPARTA trial (NCT03175224).¹

Preliminary data indicated that 6 of 14 evaluable patients achieved confirmed responses by RECIST 1.1 criteria with the agent. One patient with third-line metastatic non–small cell lung cancer (NSCLC) achieved a complete response. Five partial responses were experienced by patients with NSCLC (n = 3), pancreatic cancer (n = 1), and intrahepatic bile duct cancer (n = 1).

Moreover, the median time to response was 3.7 months and the median duration of response (DOR) was 5.6 months. The longest DOR to date is 18 months, and this patient is still on study treatment. The median progression-free survival was 4.5 months, and the median overall survival was 12.4 months.

“We are very pleased with the preliminary data showing 43% ORR in patients with non-CNS MET fusion[–positive] 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,” Guo-Liang Yu, PhD, chairman and chief executive officer of Apollomics, stated in a news release. “Alongside the Avistone data for vebreltinib in the treatment of glioblastoma with PTPRZ1 MET fusions, the clinical evidence for the efficacy of vebreltinib in MET fusions is very encouraging…We look forward to providing additional clinical updates from the SPARTA Phase 2 trial as they become available.”

The global, multicohort, single-arm, open-label, phase 2 SPARTA study is comprised of 9 cohorts²:

• Cohort A-1: Previously untreated NSCLC and exon 14 skip mutations who are naive to MET inhibition
• Cohort A-2: NSCLC and exon 14 skip mutations who previously received up to 3 lines of treatment in the unresectable or metastatic setting and were c-MET naive
• Cohort B: NSCLC and exon 14 skip mutations who received up to 3 prior lines of therapy in the unresectable or metastatic setting and were c-MET experienced
• Cohort C: A basket of tumor types, including NSCLC, upper gastrointestinal, colorectal, and hepatobiliary cancers, with MET amplification with the exception of primary CNS tumors. Patients who received prior treatment but were naive to MET inhibition or were previously untreated but refused standard therapy or treatment was unavailable or not feasible
• Cohort C-1: NSCLC with MET amplification and EGFR wild-type who received prior treatment but were naive to MET inhibition or untreated but refused standard therapy, or treatment was not available or feasible
• Cohort C-2: EGFR-positive NSCLC with acquired resistance in the form of MET amplification who had responded to a frontline EGFR inhibitor and experienced disease progression by RECIST criteria and were naive to MET inhibition
• Cohort D: A basket of tumor types except for primary CNS tumors harboring MET fusions who received prior treatment but were naive to MET inhibition or untreated but refused standard therapy, or treatment was not available or feasible
• Cohort E: Primary CNS tumors harboring MET alterations who received prior treatment but were naive to MET inhibition or untreated but refused standard therapy, or treatment was not available or feasible
• Cohort F: A basket of tumor types that were MET wild-type and had HGF and MET overexpression who received prior treatment but were naive to MET inhibition or untreated but refused standard therapy, or treatment was not available or feasible

To participate, patients needed to be at least 18 years of age, at least 1 measurable lesion, an ECOG performance status of 0 or 1, an expected survival of at least 3 months from day 1 of cycle 1 of treatment, and acceptable organ and cardiac function.

At a data cutoff date of July 31, 2024, 14 patients with non-CNS, MET fusion–positive, solid tumors were included in the study. The cohort was comprised of patients with NSCLC (n = 6), lung sarcomatoid carcinoma (n = 1), intrahepatic bile duct cancer (n = 2), colon cancer (n = 1), pancreatic cancer (n = 1), breast cancer (n = 1), head and neck cancer (n = 1), and esophageal cancer (n = 1).¹ Moreover, 2 patients had not previously received systemic treatment and the remaining 12 were receiving treatment in the second- or later-line setting.

The primary end point of the study is ORR by independent review committee (IRC) based on RECIST 1.1 criteria.² Key secondary end points include median DOR by IRC, investigator-assessed ORR and DOR, clinical benefit rate, median time to progression, PFS, and OS at 6, 12, 18, and 24 months.

Based on the early data from the trial, Apollomics, the drug developer, shared they are examining opportunities for further development of the agent in patients with tumors harboring MET fusions.¹

“Patients currently enrolled in the SPARTA MET fusion cohort will continue with treatment and study follow-up,” according to the news release.

References

1. Apoollomics 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 13, 2024. https://ir.apollomicsinc.com/news-releases/news-release-details/apollomics-announces-positive-preliminary-data-vebreltinib
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 13, 2024. https://clinicaltrials.gov/study/NCT03175224