"This simultaneous therapy and companion diagnostic approval marks an important step forward in the treatment of rare cancer and demonstrates how deep collaboration across industry partners can advance patient care.”
The FDA has granted approval to FoundationOne®CDx for use as a companion diagnostic for the identification of patients with non–small cell lung cancer (NSCLC) who may be appropriate candidates to receive capmatinib (Tabrecta), announced Foundation Medicine. The test is now approved as a companion diagnostic for 21 unique therapies.1
The MET inhibitor capmatinib, which was approved on May 6, 2020, is the only FDA-approved therapy for adult patients with metastatic NSCLC whose tumors have a MET exon 14 skipping mutation.2
“Because non-small cell lung cancer is a particularly aggressive and difficult to treat form of cancer, taking a comprehensive and validated approach to genomic testing is critical to help guide physicians’ treatment decisions,” said Brian Alexander, MD, MPH, chief medical officer, Foundation Medicine, in a statement.1 “FoundationOne CDx is a powerful tool for identifying patients with mutations that lead to MET exon 14 skipping who may be eligible for treatment with Tabrecta. This simultaneous therapy and companion diagnostic approval marks an important step forward in the treatment of rare cancer and demonstrates how deep collaboration across industry partners can advance patient care.”
FoundationOne CDx was approved under accelerated approval based on both overall response rate (ORR) and duration of response (DOR). The continued approval of this indication will be based on verification and description of the clinical benefit observed in confirmatory clinical trials. This is the only broad comprehensive genomic profiling test for all solid tumors approved by the FDA that incorporates multiple companion diagnostic claims.
About 85% of lung cancer cases are diagnosed as NSCLC, and 3% to 4% harbor the MET exon 14 skipping mutation. Prior to the indication of capmatinib, there were no other available options for this patient population.
Substitutions, insertion and deletion alterations, and copy number alterations can be detected with the next-generation sequencing-based in vitro diagnostic device, in 324 genes and select gene rearrangements, as well as genomic signatures. Microsatellite instability and tumor mutational burden can be detected by DNA isolated from formalin-fixed paraffin-embedded tumor tissue specimens.
Capmatinib received its approval from the FDA based on data from the GEOMETRY mono-I trial (NCT02414139), which is a phase II multicohort study that enrolled patients with stage IIB or IV NSCLC to receive the MET inhibitor. Data from 2 cohorts in the study were presented at the 2020 American Association for Cancer Research Annual Meeting. Cohort 4 received at least 1 prior line of therapy before entering the study (n = 69), and cohort 5 was treatment-naïve (n = 28).3
The ORR in cohort 4 was 40.6% (95% CI, 28.9%-53.1%) whereas the ORR in cohort 5b was 67.9% (95% CI, 47.6%-84.1%). The median DOR was 9.72 months in cohort 4 (95% CI, 5.55-12.98) and 11.14 months in cohort 5b (95% CI, 5.55-not evaluable), and the median progression-free survival (PFS) was 5.42 months (95% CI, 4.17-6.97) and 9.69 months (95% CI, 5.52-13.86), respectively.
The primary end point of the study was ORR, and DOR was a key secondary end point, while other secondary end points included PFS, overall survival, and safety. GEOMETRY mono-I is a 7-cohort clinical trial, which is currently recruiting patients.
Among specific criteria across the cohorts, all patients must have stage IIIB or IV NSCLC and at least 1 measurable lesion by RECIST 1.1 criteria. All patients must have recovered from all toxicities related to the previous anticancer treatment of grade ≤ 1, although patients with any grade of alopecia are eligible to enroll. They must also have adequate organ function and an ECOG performance status of 0 or 2. If patients have received prior treatment with crizotinib (Zalkori) or another cMET or HGF inhibitor, they are unable to enter the study.