The designation is based on data from the ongoing phase II VISION trial (NCT02864992), in which tepotinib demonstrated an objective response rate (ORR) of 50.0%, as assessed by an independent review committee (IRC), and an investigator-assessed ORR of 55.3%, in patients with METex14-altered NSCLC, which was identified by liquid biopsy.2 For patients who were identified to have METex14 alterations via tissue biopsy, the IRC- and investigator-assessed ORRs were 45.1% and 54.9%, respectively.
“Tepotinib was associated with robust objective responses with durability that has not previously been seen in patients with metastatic NSCLC harboring MET exon14 skipping alterations, selected by either tissue or liquid biopsy approaches,” Luciano Rossetti, global head of Research & Development for the Biopharma business of Merck KGaA, the developer of tepotinib, stated in a press release. “This breakthrough therapy designation further underscores the potential of tepotinib, and we aim to advance this program and deliver this medicine as quickly as possible to NSCLC patients who may benefit.”
MET alterations are presented in approximately 3% to 5% of all patients with NSCLC and are associated with aggressive tumor behavior and poor prognosis. Currently, there are no FDA-approved treatments that target MET alterations. Tepotinib is an investigational oral MET kinase inhibitor that is highly potent and selective.
The phase II VISION study comprised 2 cohorts: cohort A enrolled patients with METex14 skipping mutations and cohort B included those with MET amplification. In both groups, tepotinib was administered at 500 mg once daily in a 21-day cycle. In cohort A, 87 patients were enrolled and treated, with METex14 determined using liquid (n = 57) and tumor biopsy (n = 58).
The median age of patients was 74 years, and most patients (74.7%) had an ECOG performance status of 1. Brain metastases were present in 9.2% of patients. Overall, 33 patients had received no prior treatment, and 54 were treated in the second-line or beyond setting.
Results showed that the median progression-free survival was 9.5 months by IRC in liquid biopsy–assessed tumors and was 10.8 months in standard biopsy–identified tumors.
Additionally, the IRC- and investigator-assessed median duration of response (DOR) was 12.4 months and 17.1 months, respectively, among patients whose tumors were evaluated via liquid biopsy. Among patients with tissue-assessed tumors, the IRC- and investigator-assessed median DOR was 15.7 and 14.3 months, respectively.
Regarding safety, the majority of treatment-related adverse events (TRAEs) were of grade 1/2, and no grade 4/5 TRAEs were observed. All-grade TRAEs reported by ≥10% of 87 patients who were evaluable for safety included peripheral edema (48.3%), nausea (23.0%), diarrhea (20.7%), and increased blood creatinine (12.6%). Additional relevant TRAEs, the company stated, included increased lipase (4.6%), fatigue (3.4%), and vomiting (3.4%). Four patients had to permanently discontinue treatment due to TRAEs; these included peripheral edema (n = 2), interstitial lung disease (n = 1), and diarrhea and nausea (n = 1).
In March 2018, tepotinib was granted SAKIGAKE fast track designation for patients with advanced NSCLC harboring METex14 mutations by the Japanese Ministry of Health, Labor and Welfare.
A version of this article originally appeared on OncLive as “FDA Grants Tepotinib Breakthrough Designation for METex14-Altered NSCLC”
- Merck KGaA, Darmstadt, Germany, Announces FDA Breakthrough Therapy Designation for Investigational Therapy Tepotinib in Patients with Metastatic NSCLC with METex14 Skipping Alterations. Merck KGaA. Published September 11, 2019. https://prn.to/2kuDROO. Accessed September 11, 2019.
- Pain PK, Veillon R, Cortot AB, et al. Phase II study of tepotinib in NSCLC patients with METex14 mutations. J Clin Oncol. 2019;37 (suppl; abstr 9005). doi: 10.1200/JCO.2019.37.15_suppl.9005.