Capmatinib Demonstrates Clinical Meaningful Antitumor Activity in NSCLC With MET Exon 14 Skipping

Clinically meaningful antitumor activity was observed with capmatinib in patients with metastatic non–small cell lung cancer who harbor MET exon 14 skipping mutations, according to results from the phase 2 GEOMETRY mono-1 clinical trial.

Positive overall response rates (ORRs) were observed with capmatinib (Tabrecta, formerly INC280) when administered as treatment of patients with metastatic non–small cell lung cancer (NSCLC) with MET exon 14 skipping in their tumors. The agent also showed a positive duration of response (DOR), according to published findings from the phase 2 GEOMETRY mono-1 clinical trial.1,2

“The pivotal data published not only confirm the positive results we’ve seen previously with Tabrecta treatment in non-small cell lung cancer, but also underscore the value of early and broad molecular testing of patients’ tumors to guide treatment decisions for both first-line and previously treated patients," said Jeff Legos, senior vice president, head of Oncology Drug Development, Novartis Oncology.

The prospective, international, open-label, multiple-cohort, phase 2 GEOMETRY mono-1 study was launched based on preclinical evidence that single-agent capmatinib is effective for MET-dysregulated NSCLC.3-5 In the study, patients with advanced NSCLC with MET exon 14 skipping mutation or MET amplification with or without prior treatment were enrolled. The primary end point of the study was ORR, and the secondary end points were DOR, time to response, disease control, progression-free survival (PFS), safety, and pharmacokinetics.3

The study enrolled 364 patients with advanced NSCLC and 97 of them had MET exon 14 skipping, while the remaining 210 had MET amplification. The patients were divided into 7 cohorts. In cohorts 1 through 4, patients were previously treated with up to 2 prior lines of therapy. In cohorts 5a and 5b, patients were treatment naïve. Patients in cohort 6 were those with MET amplifications who had received one prior line of therapy, and cohort 7 was compiled of patients MET exon 14 skipping mutation who were treatment naïve.

Results for the MET exon 14 skipping group show that 41% (95% CI, 29-53) of the patients with who had prior treatment and 68% (95% CI, 48-84) in patients who had no prior treatment. The median DOR was 9.7 months (95%CI, 5.6-13.0) among the previously treated patients and 12.6 months (95% CI, 5.6-not estimable [NE]) among those who were treatment naïve.

“Capmatinib led to clinically meaningful antitumor activity in patients with NSCLC with a MET exon 14 skipping mutation who had not received treatment previously,” wrote the study authors led by Juergen Wolf, MD.

Wolf, MD et al noted that 14 patients in the study had brain metastases, and a post hoc analysis revealed intracranial response in 7 of those patients, 4 of which were complete responses.

The safety analysis showed that adverse events (AEs) occurred in ≥20% of patients. The most frequently reported treatment-related AEs were peripheral edema (43%), nausea (34%), increased blood creatinine (18%), and vomiting (19%). Most of the events reported were grades 1 and 2, in severity.

Capmatinib is a highly selective MET inhibitor. The agent is used predominantly for the treatment of metastatic disease in patients who cannot undergo surgery and those with an abnormal MET gene in their tumors.

“The GEOMETRY mono-1 study results published in The New England Journal of Medicine further highlight the clinical benefit that Tabrecta can provide to patients with metastatic MET exon 14-positive NSCLC,” said Steven Stein, MD, chief medical officer, Incyte.2 “Having a therapy that targets a recognized oncogenic driver offers a much-needed treatment option for patients living with this aggressive form of lung cancer and we are proud that the world-class discovery program at Incyte contributed to the fulfillment of this unmet medical need.”


1. Novartis announces NEJM publication of pivotal study of Tabrecta™ in patients with METex14 metastatic non-small cell lung cancer. News release. Novartis. September 2, 2020. Accessed September 3, 2020.

2. Incyte announces pivotal GEOMETRY mono-1 study results of capmatinib (tabrecta™) in patients with metex14 metastatic non-small cell lung cancer published in NEJM. New release. Incyte. September 2, 2020. Accessed September 3, 2020.

3. Wolf J, Seto T, Han JY, et al. Capmatinib in MET exon 14–mutated or met-amplified non–small-cell lung cancer. N Engl J Med. 2020; 383(10):944-957. doi: 10.1056/NEJMoa2002787

4. Schuler M, Berardi R, Lim W-T, et al. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial. Ann Oncol. 2020; 31:789-97.

5. Wu Y-L, Zhang L, Kim D-W, et al. Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer. J Clin Oncol. 2018; 36: 3101-9.