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The European Commission has approved capmatinib as a single agent for the treatment of patients with MET exon14 skipping–altered advanced non–small cell lung cancer who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The European Commission has approved capmatinib (Tabrecta) as a single agent for the treatment of patients with MET exon14 skipping (METex14)–altered advanced non–small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.1
The regulatory decision was based on findings from the phase 2 GEOMETRY mono-1 trial (NCT02414139), which demonstrated a confirmed overall response rate (ORR) of 51.6% (95% CI, 33.1%-69.8%) with capmatinib as second- (n = 30) or later-line (n = 1) therapy and 44% (95% CI, 34.1%-54.3%) in all pretreated patients (n = 100) with advanced METex14-altered NSCLC.
The approval comes after a positive opinion was issued in April by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency and is applicable to all 27 European Union member states plus Iceland, Norway, and Liechtenstein.
“Patients with METex14 skipping alterations typically have a more advanced form of lung cancer that is often associated with a poor prognosis and limited response to standard therapy, including immunotherapy,” Juergen Wolf, MD, of the Center for Integrated Oncology at the University Hospital Cologne in Germany, and lead investigator of the GEOMETRY mono-1 trial said in a news release. “With the approval of Tabrecta in Europe, supported by advances in biomarker testing that can help doctors direct treatment more precisely, patients with this specific genomic profile have a new targeted treatment option that can lead to improved outcomes.”
The study enrolled patients at least 18 years of age with stage IIIB or IV METex14-altered NSCLC.2 Patients had to have an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria and needed to have EGFR wild-type disease and test negative for ALK rearrangements.
Patients received 400 mg of capmatinib twice daily and were stratified into 7 cohorts based on prior lines of therapy and MET status.
Cohort 4 included pretreated patients who were receiving the agent as second- or third-line therapy (n = 69); cohort 5b included treatment-naïve patients who were receiving capmatinib in the first-line setting (n = 28); cohort 6 consisted of pretreated patients who were receiving the agent in the second-line setting (n = 31), and cohort 7 included treatment-naïve patients who were receiving capmatinib in the frontline setting (n = 32).
The primary end point of the trial was ORR per blinded independent review committee (BIRC), and a key secondary end point was duration of response (DOR) per BIRC. Other secondary end points included disease control rate per BIRC and investigator assessment, investigator-assessed DOR and ORR, time to response and progression-free survival per BICR and investigator, overall survival (OS), safety, and pharmacokinetics.
By the data cutoff of September 18, 2020, 160 patients were enrolled in the 4 cohorts; 60 patients were treatment naïve and 100 were pretreated. Notably, 31.7% of those who were treatment naïve and 14.0% of those who were pretreated were still receiving capmatinib. The most common reason for discontinuation was disease progression.
The median patient age was 71 years (range, 48-90). Most patients were female (60.6%), Caucasian (76.9%), had an ECOG performance status of at least 1 (75.0%), were never smokers (60.6%), and had adenocarcinoma (82.5%). Moreover, 16.3% of patients had brain metastases.
Additional results reflected a median OS of 13.6 months (95% CI, 8.6-22.2) in cohort 4.
In terms of safety, capmatinib displayed an acceptable toxicity profile with no new signals reported. Of the 373 patients included in all cohorts, 98.4% of patients experienced an any-grade toxicity.
The most common adverse effects (AEs) included peripheral edema (54.2%), nausea (45.0%), vomiting (28.2%), increased blood creatinine (26.5%), dyspnea (23.3%), fatigue (22.3%), and decreased appetite (21.2%).
Most patients (86.9%) experienced treatment-related AEs, the most common of which were peripheral edema (46.1%) and nausea (34.3%). Any-grade serious AEs (SAEs) occurred in 50.9% of patients, with 13.1% of those expected to be related to capmatinib.
Approximately 16% (16.1%) of patients experienced AEs that led to treatment discontinuation. Four patients experienced fatal SAEs including cardiac arrest (0.3%), hepatitis (0.3%), organizing pneumonia (0.3%), and pneumonitis (0.3%).
“As the leading cause of cancer-related deaths worldwide, lung cancer can be a devastating diagnosis for patients and their families,” Marie-France Tschudin, president of Innovative Medicines International and chief commercial officer of Novartis said. “With this new targeted therapy that treats a specific mutation driving cancer growth, we are delivering a much-needed treatment option and bringing hope to patients with this challenging disease.”