“We are pleased that the FDA has approved Tabrecta for patients with METex14 NSCLC. Having a therapy that targets the recognized oncogenic driver will provide a much needed treatment option for patients with METex14 NSCLC who currently have limited treatment options.”
The FDA granted approval to capmatinib (Tabrecta) for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.1
Capmatinib was previously granted Priority Review by the FDA in February 2020 for this indication based on results from the GEOMETRY mono-I trial (NCT02414139), which is evaluating the MET inhibitor in 97 patients with metastatic NSCLC with confirmed MET exon 14 skipping mutations.
“We are pleased that the FDA has approved Tabrecta for patients with METex14 NSCLC,” said Steven Stein, MD, chief medical officer, Incyte, in a statement. “Having a therapy that targets the recognized oncogenic driver will provide a much needed treatment option for patients with METex14 NSCLC who currently have limited treatment options.”
At the recent 2020 American Association for Research Annual Meeting, results were presented for 2 cohorts of the 7-cohort trial. Cohort 4 consists of 69 patients who received at least 1 prior line of therapy for advanced disease and cohort 5 was compiled of 28 patients who were treatment naïve.2
The overall response rate per blinded independent review committee (BIRC) for cohort 4 was 40.6% (95% CI, 28.9%-53.1%) and for the 5b cohort, the objective response rate (ORR) was 67.9% (95% CI, 47.6%-84.1%). In cohorts 4 and 5b, respectively, the median duration of response (DOR) was 9.72 months (95% CI, 5.55-12.98) and 11.14 months (95% CI, 5.55-not evaluable). The median progression-free survival (PFS) observed in the 2 cohorts was 5.42 months (95% CI, 4.17-6.97) and 9.69 months (95% CI, 5.52-13.86), respectively.
Preliminary intracranial responses were observed in 54% of the patients (7 of 13) with brain metastases.
The phase II multicohort study enrolled patients with stage IIIB or IV NSCLC who had an ECOG performance status of 0 or 1. Tumors had to be EGFR wild-type, ALK-negative, and have MET dysregulation for the patient to be included in the study. All patients received 400 mg of capmatinib twice daily.
The key secondary end point was duration of response (DOR), and other secondary end points included PFS, overall survival, and safety.
Cohort 4 had an ORR of 42.0% (95% CI, 30.2%-54.5%), and the disease control rate (DCR) was 78.3% (95% CI, 66.7%-87.3%) by BIRC and 76.8% (95% CI, 65.1%-86.1%) by investigator assessment. The ORR in cohort 5b was 60.7% (95% CI, 40.6%-78.5%), and the DCR was 96.4% (95% CI, 81.7%-99.9%) by BIRC and 96.4% (95% CI, 81.7%-99.9%) by investigator assessment.
Of the 13 evaluable patients with brain metastases at baseline, 4 had complete resolution of all brain lesions. One patient had complete resolution in 3 lesions with stabilization in 4, another patient had complete resolution in 2 lesions with stabilization in 1, and 1 patient had complete resolution in 1 lesion with stabilization in 3.
Overall, 35.6% of patients had experienced grade 3/4 adverse events (AEs), and 12.9% of patients had serious treatment-related AEs. The most common AE was peripheral edema, which occurred in all-grade severity in 41.6% of patients and as grade 3/4 in 7.5% of patients. Investigations reported there were no treatment-related deaths.
Approximately 21.9% of patients received a dose reduction, and 11.1% discontinued treatment due to treatment-related AEs. The most common causes for treatment discontinuation (≥1%) were peripheral edema (1.8%), pneumonitis (1.5%), and fatigue (1.5%).
This approval fills a gap in the treatment landscape for NSCLC as there have been no other approvals for therapies targeting the MET exon 14 mutation in advanced NSCLC. This mutation is known to occur in approximately 3% to 4% of patients with newly diagnosed NSCLC and is considered an oncogenic driver.