Capmatinib shows potential for treatment of MET-driven NSCLC
medwireNews: The selective MET inhibitor capmatinib has antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, including in those with brain metastases, suggest GEOMETRY mono-1 study results.
Edward Garon (University of California, Los Angeles, USA) – who presented the phase 2 trial data at the 2020 AACR Virtual Annual Meeting I – said that capmatinib showed “clinically meaningful efficacy” in this patient population, which typically has “both poor prognosis and poor responses to standard therapies including immunotherapy.”
He reported on two cohorts of the trial, specifically cohorts 4 and 5b, which enrolled previously treated (n=69) or treatment-naïve (n=28) individuals, respectively, with stage IIIB–IV NSCLC that was wild-type for ALK and EGFR, but positive for MET exon 14 mutations.
Overall, treatment with capmatinib 400 mg twice daily led to an independently assessed objective response rate of 40.6% in the previously treated cohort and 67.9% in the treatment-naïve cohort, with median durations of response of 9.72 and 11.14 months, respectively. The disease control rates were a corresponding 78.3% and 96.4%.
There were 13 evaluable patients in the two cohorts with brain metastases at baseline, and just over half (54%) achieved an intracranial response. Four patients experienced complete resolution of all lesions, while the remaining three patients achieved complete resolution of at least one lesion and stabilization of the other lesions. All but one patient achieved intracranial disease control.
“Further validation of the intracranial efficacy of capmatinib is warranted,” said Garon.
He also presented safety data based on the 334 participants currently enrolled across the seven cohorts of the trial, which showed “a manageable safety profile” for the MET inhibitor in this “largest database of MET dysregulated NSCLC patients” at present.
Treatment-related adverse events (TRAEs) of grade 3 or 4 were reported by 35.6% of capmatinib-treated patients, with peripheral edema (7.5%) and fatigue (3.0%) the most common events of this severity. Garon highlighted, however, that grade 4 events tended to be “rare,” observed in just 4.5% of participants.
Dose reductions as a result of TRAEs were required by 21.9% of patients, while 11.1% discontinued due to a TRAE.
Discussant Taofeek Owonikoko, from Emory University in Atlanta, Georgia, USA, commented that the study provides evidence that “capmatinib is an effective targeted therapy against MET-driven tumors,” with “an overall positive safety profile” and “a very encouraging signal of efficacy against intracranial metastases.”
He highlighted that “future basic and translational research work will be needed to further understand the mechanisms of resistance and inform combination strategies.”
Owonikoko continued: “Currently available data would suggest that antiangiogenic, immune checkpoint, and anti-EGFR or anti-RAS agents would be suitable partners for enhanced efficacy.”
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