Capmatinib (Tabrecta), an oral kinase inhibitor, has shown clinical activity in patients with high-level MET-amplified advanced non–small-cell lung cancer (NSCLC), according to new data presented at the ASCO 2020 virtual annual meeting. In the phase 2 GEOMETRY mono-1 study, nearly 30% of patients who previously received systemic therapy and 40% of treatment-naïve patients had a response to capmatinib, reported Juergen Wolf, MD, Lung Cancer Group Cologne, Center for Integrated Oncology, University Hospital Cologne, Germany.
The median progression-free survival was 4.07 months in pretreated patients and 4.17 months in treatment-naïve patients, and the median overall survival was 10.6 months in pretreated patients and 9.6 months in the treatment-naïve group.
The ongoing phase 2 multicohort, multicenter GEOMETRY mono-1 study had previously shown rapid, deep, and durable responses with capmatinib in patients with advanced NSCLC harboring mutations leading to MET exon 14 skipping. The response rate in the first-line treatment was 68% compared with 40.6% in the second- and third-line treatments, respectively.
First Met-Directed Therapy for NSCLC
Previous efficacy data of capmatinib in the setting of MET exon 14 skipping NSCLC led to the FDA accelerated approval of capmatinib on May 6, 2020, for the treatment of adults with metastatic NSCLC whose tumors harbor mutations leading to MET exon 14 skipping. Capmatinib is the first MET-directed agent approved by the FDA for the treatment of NSCLC with MET exon 14 skipping.
The current analysis presented at the meeting was focused on patients with MET amplification but without mutations leading to MET exon 14 skipping. In this analysis, “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) suggests that this patient population may benefit from a MET-directed treatment such as capmatinib.
“The promising ORRs observed in the gene copy number ≥10 cohorts suggest that this group of patients may benefit from MET-directed therapy.” The subgroup experiencing a benefit from MET-directed therapy should be characterized more precisely in the future, he believes.
The efficacy and safety of capmatinib were investigated 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 and 5a of the study recruited patients with stage IIB/IV MET-amplified NSCLC of any histology with gene copy number ≥10. Patients received capmatinib 400 mg twice daily. No patient in either cohort could have mutations leading to MET exon 14 skipping. Cohort 1a consisted of 69 patients and cohort 5a comprised 15 patients.
The median age of the treatment-naïve cohort was 70 years versus 60 years in the cohort of patients who had received previous treatment. Approximately 70% of all the patients were white, and 27.4% were Asian. Approximately 90% were current or former smokers and approximately 25% were female.
Approximately 33% 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% in the pretreated cohort, with 1 (1.4%) complete response and 19 (27.5%) partial responses. By investigator assessment, the ORR in this cohort was 27.5%.
The ORR in the treatment-naïve cohort was 40%. There were no complete responses in this cohort and 6 partial responses, by independent review and by investigator assessment.
Responses were deep in the majority of patients across both cohorts, 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 treatment-naïve patients.
The most common adverse events across all cohorts were peripheral edema (51.1%), nausea (35.9%), and vomiting (20.6%). Most adverse events were grade 1 or 2, and 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.