The Japanese Ministry of Health, Labor, and Welfare has approved capmatinib for patients with MET exon 14 skipping mutation–positive advanced and/or recurrent unresectable non–small cell lung cancer.
The Japanese Ministry of Health, Labor, and Welfare (MHLW) has approved capmatinib (Tabrecta; formerly INC280) for patients with MET exon 14 skipping (METex14) mutation–positive advanced and/or recurrent unresectable non–small cell lung cancer (NSCLC), according to Novartis, the drug developer.1
“With the remarkable overall response rates seen both in treatment-naïve and previously treated patients, we are thrilled that MHLW had added [capmatinib] as a new treatment option for patients with advanced NSCLC with METex14,” Brian Gladsden, president of Novartis Oncology Japan, said in a press release. “Today’s approval reinforces the potential benefit this new MET inhibitor can bring to thousands of patients diagnosed in Japan each year and is a positive step in our journey to transform the lives of patients with lung cancer.”
The regulatory decision was based on data from the pivotal phase 2 GEOMETRY mono-1 trial. Results showed of 97 patients with METex14 mutations, the confirmed overall response rate (ORR) per blinded independent review committee and via RECIST v1.1 criteria was 68% (95% CI, 48-84) in 28 treatment-naïve patients and 41% (95% CI, 29-53) in 69 patients who received previous treatment.
Furthermore, the median duration of response with capmatinib was 12.6 months (95% CI, 5.5-25.3) in those who were treatment-naïve versus 9.7 months (95% CI, 5.5-13.0) in those who received prior treatment; there were 19 versus 28 responders, respectively.
Capmatinib is being evaluated across several cohorts of the GEOMETRY trial. Initial data from cohorts 4a and 5b had been reported during the 2019 ASCO Annual Meeting. Cohort 4 enrolled pretreated patients whose tumors harbored METex14 alterations in the second- or third-line setting (n = 69), and cohort 5b was comprised of treatment-naïve patients (n = 28).
The median age across the cohorts analyzed was 71 years, with the majority of patients, or 75%, having an ECOG performance score of 1. In cohort 4, 15.9% of patients had brain metastases compared with 10.7% of those enrolled on cohort 5b. The most common prior treatment received as platinum-based chemotherapy (88.4%).
In those who were pretreated, the ORR by independent review with the agent was 40.6% (95% CI, 28.9%-53.1%). The disease control rate (DCR) with capmatinib was 78.3% (95% CI, 66.7%-87.3%). In treatment-naïve patients, the ORR by independent review was 67.9% (95% CI, 47.6%-84.1%) and the DCR was 96.4% (95% CI, 81.7%-99.9%).2
Fifty-four percent of patients with brain metastases at baseline were found to have achieved an intracranial response with capmatinib (n = 7/13). Notably, 31% of these patients experienced complete resolution of brain lesions (n = 4). Moreover, the intracranial DCR was 92.3% with the agent (n = 12/13).
During the 2020 ASCO Virtual Scientific Program, investigators reported safety and efficacy data with the agent in patients with high-level MET-amplified (defined as GCN ≥10) advanced NSCLC who were either pretreated with 1 or 2 prior lines of systemic therapy (cohort 1a) or who were treatment-naïve (cohort 5a). Results showed that capmatinib showcased evidence of activity in patients with high-level MET-amplified (defined as GCN ≥10); however, response rates were more moderate compared with METex14 cohorts in the respective treatment lines.3
Specifically, the best ORR in cohort 1a (n = 69) by blinded independent review committee (BIRC) was 29.0% (95% CI, 18.7-41.2) and 27.5% (95% CI, 17.5-39.6) by investigator versus 40.0% (95% CI, 16.3-67.7) and 40.0% (95% CI, 16.3-67.7), respectively in cohort 5a (n = 15). The DCR in cohort 1a was 71.0% (95% CI, 58.8-81.3) and 60.9% (95% CI, 48.4-72.4), respectively, and 66.7% (95% CI, 38.4-88.2) and 73.3% (95% CI, 44.9-92.2), respectively.
The median DOR in cohort 1a was 8.31 months (95% CI, 4.17-15.44) via BIRC and 6.80 months (95% CI, 4.21-20.73) per investigator; the median DOR was 7.54 months (95% CI, 2.56-14.26) and 9.66 (95% CI, 4.01-17.08), respectively.
The median progression-free survival (PFS) with capmatinib was 4.07 months (95% CI, 2.86-4.83) via BIRC and 4.14 months (95% CI, 2.79-5.52) via investigator in cohort 1a. In cohort 5a, median PFS via BIRC and investigator was 4.17 months (95% CI, 1.45-6.87) and 2.76 (95% CI, 1.45-6.87), respectively. Overall survival was 10.61 months (95% CI, 6.28-17.22) in cohort 1a and 9.56 months (95% CI, 4.80–nonevaluable) in cohort 5a.
Results from cohort 6, which was comprised of patients with either MET GCN ≥10 or METex14 who had received 1 prior line of treatment, were also presented at the meeting.4 Notably, this was the first cohort in which the agent was given without fasting restrictions. Here, results showed that the agent had efficacy in patients with NSCLC whose tumors harbored METex14 alterations. Although no responses were observed in patients with MET GCN ≥10, all patients had stable disease per BIRC assessment.
Capmatinib was approved by the FDA in May 2020 for use in patients with metastatic METex14-mutated NSCLC based on primary findings from the GEOMETRY mono-1 trial. The FDA simultaneously approved the FoundationOne CDx assay (F1CDx) for use as a companion diagnostic for the agent to detect tumor mutations that can led to METex14. The diagnostic was also approved in Japan by the MHLW on May 25, 2020.