Tepotinib monotherapy induced promising objective response rates (ORRs) with a tolerable safety profile in patients with advanced non-small cell lung cancer (NSCLC) with a MET exon 14 skipping mutation (METex14), according to results from cohort A of the phase 2 VISION study presented at the 2020 World Conference on Lung Cancer in Singapore.
METex14 skipping mutations occur in approximately 3% to 4% of patients with NSCLC and cause constitutive activation of the MET signaling pathway. Tepotinib inhibits MET with high selectivity. The aim of cohort A of the VISION trial (NCT02864992) was to evaluate the safety and efficacy of tepotinib in this patient population.
Cohort A enrolled 152 patients with advanced NSCLC and a METex14 skipping mutation, all of whom received single-agent tepotinib. Patients were eligible to enroll on the VISION trial if they had treatment-naïve disease or had received 1 or 2 prior lines of therapy, including immunotherapy. The primary end point was ORR. Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and safety.
At baseline, the median patient age was 73.1 years and 52% were male; 71.1% were White and 25.0% were Asian. Fifty-two percent of patients had a smoking history. The majority of patients had adenocarcinoma histology at (86.2%); 9.9% had squamous histology. Brain metastases were present among 15.1% of patients at baseline. Fifty-four percent of patients had received prior therapy.
The ORR was 44.7% and was similar among patients with treatment-naïve (44.9%) and those who had received prior therapy (44.6%). There were no complete responses. The median DOR was 11.1 months, which was also similar regardless of prior therapy (treatment-naïve, 10.8 months; previously treated, 11.1 months).
The median PFS was 8.9 months. Among patients with treatment-naïve or previously treated disease, the median PFS was 8.5 months and 10.9 months, respectively.
Grade 3 or higher adverse events (AEs) occurred among 25% of patients and led to treatment discontinuation in 11%, treatment interruption in 35%, and dose reduction in 28%. The most common treatment-related AEs were peripheral edema, nausea, diarrhea, and blood creatinine elevation.
“Tepotinib demonstrated durable clinical activity, across therapy lines, in patients with MET exon 14 skipping NSCLC, as expected when targeting an oncogenic driver alteration,” concluded Paul K. Paik, MD, who presented the updated findings.
Disclosures: Paul K. Paik, MD, disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Paik PK, Sakai H, Felip E, et al. Tepotinib in patients with MET exon 14 (METex14) skipping advanced NSCLC: updated efficacy results from VISION cohort A. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2020. Abstract 1361.