Home World News Robust and Durable Clinical Activity of Tepotinib in Patients with METex14-Skipping NSCLC

World News

Robust and Durable Clinical Activity of Tepotinib in Patients with METex14-Skipping NSCLC

June 21, 2023

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In a long-term follow-up analysis of data from the phase II VISION non-randomised study, tepotinib demonstrated robust and durable clinical outcomes across therapy lines in the largest known clinical trial of patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC). Efficacy was clinically meaningful in patients with one or more prior therapies, and particularly in treatment-naive patients. Tepotinib was generally well tolerated.

The findings from an analysis after at least 18 months of follow-up in cohort C are published on 4 June 2023 by Dr. Julien Mazieres of the Service de pneumologie, Hôpital Larrey, CHU de Toulouse, Université Paul Sabatier in Toulouse, France, and study colleagues in the JAMA Oncology that coincided with a poster presentation by Dr. Paul K. Paik of the Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center in New York, NY, US at 2023 ASCO Annual Meeting in Chicago, IL, US.

Cohort A from the VISION demonstrated robust and durable clinical activity with tepotinib in patients with METex14-skipping NSCLC, based on which, tepotinib was approved for use in several countries. The authors now report in JAMA Oncology a follow-up analysis of the independent similar findings from cohort C of the VISION study along with the combined cohorts A and C outcomes after at least 18 months of follow-up. Cohort C was an independent cohort, designed to confirm findings from cohort A. Data cut-off was 20 November 2022.

Patients received tepotinib, 500 mg (450 mg active moiety), once daily. The primary endpoint was objective response by independent review committee according to RECIST v1.1. Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.

Cohorts A and C included 313 patients, of whom 50.8% were female, 33.9% Asian; median age was 72 years (range, 41-94 years). The objective response rate (ORR) was 51.4% (95% confidence interval [CI] 45.8%-57.1%) with a median DoR of 18.0 months (95% CI 12.4-46.4). In cohort C comprising 161 patients, an ORR of 55.9% (95% CI 47.9%-63.7%) with a median DoR of 20.8 months (95% CI 12.6-not estimable [NE]) was reported across treatment lines, comparable to cohort A comprising 152 patients. In 164 treatment-naive patients in cohorts A and C, ORR was 57.3% (95% CI 49.4%-65.0%) and median DoR was 46.4 months (95% CI 13.8-NE). In 149 previously treated patients, ORR was 45.0% (95% CI 36.8%-53.3%) and median DoR was 12.6 months (95% CI 9.5-18.5).

In patients with baseline brain metastases, tepotinib demonstrated robust systemic and intracranial outcomes, which had comparable clinical benefit to patients without baseline brain metastases.

The most common treatment-related adverse event (TRAE) was peripheral oedema that occurred in 210 patients (67.1%), of whom 35 patients (11.2%) experienced grade ≥3 events. Other TRAEs occurring in more than 20% of patients included hypoalbuminemia (23.6%), nausea (23.3%), diarrhoea (22.4%), and increase in blood creatinine level (22.0%), but were mostly grades 1 to 2.

The authors concluded that outcomes from the independent cohort C of the VISION study support the positive outcomes of tepotinib first reported in cohort A, which now has follow-up of more than 35 months. With updated results from a larger patient population, ORR increased, particularly in treatment-naive patients. Tepotinib demonstrated clinically meaningful outcomes both in treatment-naive and pretreated patients with METex14-skipping NSCLC, particularly when considering outcomes with non-targeted therapies.

The study was sponsored by the healthcare business of Merck KGaA, Darmstadt, Germany.