FDA Grants Regular Approval to Capmatinib for METex14+ NSCLC

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The FDA has granted regular approval to capmatinib (Tabrecta) for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to MET exon 14 skipping, as detected by an FDA-approved test.

On May 6, 2020, capmatinib was granted accelerated approval for the same indication. The regulatory decision was based on initial data pertaining to overall response rate (ORR) and duration of response (DOR) with the agent, which had been reported in the phase 2 GEOMETRY mono-1 trial (NCT02414139).

Specifically, the agent elicited an ORR of 67.9% (95% CI, 47.6%-84.1%) by independent review in those with treatment-naïve disease; this rate was 40.6% (95% CI, 28.9%-53.1%) in pretreated patients. The disease control rates in the treatment-naïve and pretreated patients were 78.3% (95% CI, 66.7%-87.3%) and 96.4% (95% CI, 81.7%-99.9%), respectively.

The conversion to regular approval was based on findings from an additional 63 patients, as well as an additional 22 months of follow-up that allowed for investigators to examine durability of response and confirm the clinical benefit achieved with capmatinib.

The multicenter, non-randomized, open-label, multicohort GEOMETRY mono-1 trial enrolled patients with NSCLC whose tumors harbored a mutation that leads to MET exon 14 skipping.3

Patients were required to have EGFR wild-type and ALK-negative status, and at least 1 measurable lesion per RECIST v1.1 criteria. THose with symptomatic central nervous system (CNS) metastases, clinically significant uncontrolled cardiac disease, or who had received any MET or HGR inhibitor were excluded.

Study participants received oral capmatinib at a twice-daily dose of 400 mg until disease progression or intolerable toxicity. ORR by blinded independent review committee (BIRC) and RECIST v1.1 criteria served as the major efficacy outcome measure. An additional efficacy outcome measure of interest was DOR by BIRC.

The efficacy population was comprised of 60 treatment-naïve and 100 previously treated patients. The median age of these patients was 71 years (range, 48-90). The majority of patients were female (61%), White (77%) White; and had an ECOG performance status of 1 (74%). Additionally, 61% of patients were never smokers, 83% had adenocarcinoma, and 16% had CNS metastases.

Among previously treated patients, 81% received one, 16% received two and 3% received three prior lines of systemic treatment. In this population, 86% previously received platinum-based chemotherapy.

Data showed that among the treatment-naïve patients, capmatinib elicited an ORR of 68% (95% CI, 55%-80%), which included a complete response rate of 5% and a partial response (PR) rate of 63%. In this group, the median DOR with capmatinib was 16.6 months (95% CI, 8.4-22.1), and 49% of patients had a DOR of at least 12 months.

Among the previously treated patients, the ORR achieved with capmatinib was 44% (95% CI, 34%-54%), which included a PR rate of 44%. These patients expereinced a median DOR of 9.7 months (95% CI, 5.6-13), with 36% experiencing a DOR that lasted for 12 months or longer.

The most frequently reported adverse effects that occurred in at least 20% of patients were edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.

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