Capmatinib, a new agent that targets MET, demonstrated strong clinical benefit with nearly three-fourths of patients who were previously untreated for METΔex14 mutated advanced non-small cell lung cancer (NSCLC) showing a response following four months of oral capmatinib (INC280) therapy, according to results reported at the ESMO 2018 Congress in Munich, Germany. Patients who had received prior treatment for advanced METΔex14 mutated NSCLC also demonstrated a response to capmatinib.
Juergen Wolf of the Centre for Integrated Oncology, University Hospital Cologne in Cologne, Germany presented findings on behalf of colleagues from the phase II GEOMETRY mono-1 study (NCT02414139), which assessed the response to treatment with capmatinib in both pretreated and treatment naïve patients with advanced NSCLC and METΔex14 mutations.
Capmatinib is an orally available highly potent and selective inhibitor of MET, which has a key role in tumour cell proliferation, survival, invasion, metastasis, as well as tumour angiogenesis.
MET mutations leading to exon 14 deletion (METΔex14) have been observed in approximately 3 to 4% of patients with NSCLC.
Professor Wolf reported the results of cohorts 4 and 5b of the study at ESMO 2018. Both of these cohorts comprised patients with centrally confirmed METΔex14 mutated or MET amplified advanced NSCLC; cohort 4 patients had received 1 to 2 prior lines of therapy and cohort 5b patients were treatment-naïve.
All patients were ≥18 years of age, with ECOG PS 0 or 1 and had ALK and EGFR wild-type, stage IIIB/IV NSCLC of any histology.
The patients were treated with capmatinib tablets at 400 mg twice daily.
The primary endpoint was overall response rate (ORR) by blinded independent central review (BIRC) per RECIST v1.1. The key secondary endpoint was duration of response (DoR) by BIRC.
Treatment naïve patients demonstrated a much greater response to capmatinib
At a follow-up of 18 weeks or more, 69 cohort 4 and 25 cohort 5b patients had available data and were included in the analysis. The confirmed ORR was 39.1% (95% confidence interval [CI], 27.6 - 51.6) in cohort 4, and 72.0% (95% CI, 50.6 - 87.9) in cohort 5b.
At this time, treatment was ongoing for 20.3% of cohort 4 patients and 44.0% of cohort 5b patients.
Preliminary activity in patients with brain metastases was also observed.
At a median follow-up of 5.6 months, DoR data were not mature.
Capmatinib adverse events were mostly mild to moderate
The most frequently reported adverse events (AEs) of any grade irrespective of causality that occurred ≥ 20% of patients across 302 patients in all six cohorts of the trial included peripheral oedema in 49.0% of patients, nausea in 43.4%, vomiting in 28.5%, blood creatinine increased in 24.5%, and dyspnoea in 24.2% of patients. Decreased appetite (21.2%) and fatigue (20.9%) were also reported in 21.2% and 20.9% of patients, respectively.
Most of the AEs were grades 1/2.
Capmatinib demonstrated a manageable toxicity profile in treatment naïve patients with NSCLC and METΔex14 mutation, which according to Professor Wolf, constitutes a challenging patient population. Capmatinib treatment demonstrated a clinically meaningful objective response rate of 72% by BIRC in treatment naïve patients.
The investigators noted that the differential benefit that was observed between patients receiving capmatinib as first-line and as second line and beyond, suggests a need for earlier diagnostic testing and prompt first-line treatment for optimal capmatinib benefit.
This trial was sponsored by Novartis.
LBA52 – Wolf J, Seto T, Han J-Y, et al. Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC).