Tepotinib, a once-daily highly selective oral MET inhibitor, has previously shown clinical activity in patients with MET-driven tumors.1 In a new open-label, phase 2 study, researchers found that administering the drug yielded a partial response in nearly half of patients with non–small cell lung cancer (NSCLC) and MET exon 14 skipping mutations, which occur in 3% to 4% percent of patients with the condition.2
Study participants were 18 years or older and had histologically or cytologically confirmed, locally advanced or metastatic NSCLC with MET exon 14 skipping mutations. The researchers performed prospective testing of MET exon 14 skipping mutations using circulating free DNA collected from plasma or by examining RNA collected from fresh or archival tumor-biopsy tissue.
The investigators’ primary goal was to assess a confirmed objective response, either partial or complete, according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Response for the primary endpoint was assessed by an independent review committee.
Secondary endpoints included objective response, duration of response, progression-free survival, and overall survival; all endpoints were assessed by the study authors. The investigators also evaluated patient-reported outcomes using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Modules 13 and 30 (EORTC QLQ-LC13 and EORTC QLQ-C30) and the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). The investigators examined adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
The researchers divided the study sample into 3 groups: a liquid-biopsy group, a tissue-biopsy group, and a combined group that included either biopsy method.
The investigators prescreened 6708 patients for MET alterations. Then 169 patients with MET exon 14 skipping mutations were screened. Of these patients, 152 were given a dose of 500 mg of tepotinib once daily and were considered to be the safety population, and 99 were followed for at least 9 months — a group considered the efficacy population.
In the efficacy group, the median patient age was 74 years. Moreover, 46% of the patients in the group had a history of smoking, and 97% had metastatic disease when they entered the study. Of all the patients in the group, 56 had undergone previous treatment.
Patients were treated with tepotinib for the median period of 6.9 months (range, <0.1-36.7). The patients in the efficacy population were followed for the median period of 17.4 months, whereas the patients in the safety population were followed for a median of 11.8 months (range, 0.3-37.1).
In the efficacy population, the objective response rate was 46% (95% CI, 36-57), according to independent review. No patients had a complete response; all of the responses seen were partial responses.
According to investigator assessment, the response rate was 56% (95% CI, 45-66) in the efficacy population, with 2 patients who had a complete response and 53 patients who had a partial response. Most patients experienced tumor shrinkage, with 89% as determined by independent review and 88% as evaluated by investigators. Response onset occurred rapidly, typically within 6 weeks after the initiation of treatment.