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Capmatinib Shows Activity in MET-Amplified Non–Small-Cell Lung Cancer

December 15, 2020 | Web Exclusives | Lung Cancer

According to information reported by Juergen Wolf, MD, Lung Cancer Group Cologne, Center for Integrated Oncology, University Hospital Cologne, Germany, nearly 30% of patients who previously received systemic therapy and 40% of previously untreated patients participating in the phase 2 GEOMETRY mono-1 study had a response to capmatinib.

Pretreated patients had a median progression-free survival (PFS) of 4.07 months, whereas treatment-naïve patients had a PFS of 4.17 months. Median overall survival was 10.6 months in pretreated patients and 9.6 months in the treatment-naïve group.

The phase 2 multicohort, multicenter GEOMETRY mono-1 study had previously shown rapid, deep, and durable responses with capmatinib in patients with advanced non–small-cell lung cancer (NSCLC) with mutations leading to MET exon 14 skipping. The first-line treatment response rate was 68% compared with 40.6% in the second- and third-line treatments.

Novel MET-Directed Therapy for NSCLC

Previous efficacy data of capmatinib from patients with MET exon 14 skipping NSCLC led the FDA to accelerate the approval of capmatinib for the treatment of adults with metastatic NSCLC whose tumors have mutations leading to MET exon 14 skipping, making it the first MET-directed agent approved by the FDA for the treatment of NSCLC with MET exon 14 skipping.

MET-Amplified NSCLC

The data presented at the meeting were focused on patients with MET amplification but without mutations leading to MET exon 14 skipping. Capmatinib “showed evidence of activity in patients with high-level MET amplification [ie, gene copy number ≥10], although the response rates were moderate compared with MET exon 14 cohorts in their respective treatment lines,” Dr Wolf said.

He noted that the objective response rate (ORR) seen in the gene copy number ≥10 cohorts suggests they may benefit from a MET-directed treatment such as capmatinib. He also said that the subgroup experiencing a benefit from MET-directed therapy should be characterized more precisely in the future.

Researchers investigated the efficacy and safety of capmatinib in patients with high-level MET-amplified advanced NSCLC who had received 1 or 2 previous lines of systemic therapy (cohort 1a) or who were treatment naïve (cohort 5a).

Cohorts 1a (69 patients) and 5a (15 patients) featured patients with stage IIB/IV MET-amplified NSCLC of any histology with gene copy number ≥10. Patients received capmatinib 400 mg twice daily. Patients with mutations leading to MET exon 14 skipping were prohibited from either cohort.

The patients in the treatment-naïve cohort tended to be older than those in the cohort of previously treated patients (median age, 70 years vs 60 years). The majority of patients in the study were white (approximately 70%), and 27.4% were Asian. Approximately 90% were current or former smokers and approximately 25% were female.

Roughly one-third of patients in each cohort had ≥3 metastatic sites. The approximate rates of the key metastatic sites were brain (40%), adrenal (66%), bone (33%), liver (25%), and lymph node (80%).

The ORR, as determined by a blinded independent review committee, was 29.0% (compared with an investigator assessment ORR of 27.5%) in the pretreated cohort, with 1 (1.4%) complete response and 19 (27.5%) partial responses.

The treatment-naïve cohort had an ORR of 40%. There were no complete responses in this cohort and 6 partial responses, by independent review and by investigator assessment.

The majority of patients in both cohorts experienced deep responses, said Dr Wolf. The median duration of response as assessed by independent review was 8.3 months in the pretreated patients and 7.54 months in the treatment-naïve patients.

Safety

The most common adverse events across all cohorts were peripheral edema (51.1%), nausea (35.9%), and vomiting (20.6%). Although most adverse events were grade 1 or 2, more than one-third (37.6%) of patients had grade 3/4 adverse events. A total of 83 (22.8%) patients had at least 1 adverse event leading to dose reduction, and 39 (10.7%) had adverse events leading to treatment discontinuation.

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