Novartis Highlights Strong Long-Term Efficacy of Tabrecta in METex14-Mutant Metastatic NSCLC with Updated Survival Data
Jun 16, 2021 02:23
CST Updated
02:23
Novartis
Drug Development and Manufacturing
June 15, 2021 /BioonBIOON/ --Novartis(Novartis) recently reported for the first time mature overall survival (OS) and updated overall response rate (ORR) data from the pivotal Phase 2 GEOMETRY mono-1 study. The study evaluated the targeted anticancer drug Tabrecta (capmatinib) in adult patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping (METex14) mutations. The data show:In previously untreated (treatment-naïve, first-line) patients, the median OS was 20.8 months and the ORR was 65.6%.；In previously treated patients (pre-treated, second-line therapy), the median OS was 13.6 months and the ORR was 51.6%.
Tabrecta is the first therapy approved by the U.S. FDA specifically for metastatic NSCLC with MET exon 14 skipping mutations.This drug is an oral, potent, selective MET inhibitor that was granted in May 2020FDAApproved for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, including first-line (treatment-naïve) patients and previously treated patients, regardless of the type of prior therapy.
Currently, the 5-year survival rate for lung cancer is less than 20%, and this rate declines further when diagnosed at an advanced stage. Nearly one-third of patients with metastatic NSCLC harbor targetable mutations. METex14 mutations are reported to occur in 3%–4% of patients with metastatic NSCLC. Many patients with METex14-mutant NSCLC are not diagnosed until the disease has progressed to an advanced stage, often resulting in a poor prognosis.
Jürgen Wolf, Principal Investigator of the GEOMETRY mono-1 trial and from the Comprehensive Cancer Center at University Hospital Cologne, Germany, stated: “This new analysis further supports Tabrecta as a cornerstone targeted therapy for patients with METex14 NSCLC, and highlights testingBiomarkerthe importance of. The impressive overall survival and high response rate results for first-line treatment in this study willTumorclinicians provide important information for treatment decisions.”
NovartisOncologyTumorJeff Legos, Head of Drug Development and Senior Vice President, stated: “The introduction of Tabrecta a year ago significantly transformed the treatment landscape for patients with METex14 NSCLC. We now have further evidence demonstrating that Tabrecta, as a market-leading targeted therapy for METex14 NSCLC, can help prolong patient survival.”
Capmatinib Chemical Structure (Image source: medchemexpress.cn)
GEOMETRY mono-1 is a multicenter, non-randomized, open-label, multi-cohort phase 2 study, inTumorThe study was conducted in adult patients with metastatic NSCLC harboring MET exon 14 skipping mutations, who were EGFR wild-type and ALK rearrangement-negative. During the study, patients received oral Tabrecta 400 mg tablets twice daily. Patients were assigned to cohorts based on MET status and prior treatment regimens. The primary endpoint was the overall response rate (ORR) assessed by a blinded independent review committee (BIRC) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The key secondary endpoint was the duration of response (DOR) assessed by the BIRC.
The analysis presented herein includes data from the expanded treatment-naïve (first-line, 1L) cohort 7 and the previously treated (2L+) cohort 6, along with mature data from previously reported cohorts, totaling 160 patients. The analysis results provide an update on the efficacy of Tabrecta in treatment-naïve and previously treated patients with METex14 skipping metastatic NSCLC.
——Regarding ORR: (1) In treatment-naïve patients (Cohort 5b, n=28; Cohort 7, n=32), ORR was 67.9% (95% CI: 47.6-84.1) and 65.6% (95% CI: 46.8-81.4), respectively. (2) In previously treated patients (Cohort 4, n=69; Cohort 6, n=31), ORR was 40.6% (95% CI: 28.9-53.1) and 51.6% (95% CI: 33.1-69.8), respectively.
—— DOR: (1) In treatment-naïve patients (Cohort 5b, n=28; Cohort 7, n=32), DOR was 12.6 months (95% CI: 5.6–NE) and NE (95% CI: 5.5–NE), respectively. (2) In pretreated patients (Cohort 4, n=69; Cohort 6, n=31), DOR was 9.7 months (95% CI: 5.6–13.0) and 8.4 months (95% CI: 4.2–NE), respectively.
——OS: The median OS in treatment-naive patients (cohort 5b, n=28) was 20.8 months (95% CI: 12.42–NE); in previously treated patients (cohort 4, n=69), it was 13.6 months (95% CI: 8.61–22.24). In expansion cohorts 6 and 7, the median OS was not reached.
In this study, no new safety signals or unexpected safety findings were observed. The most common adverse events (>20%, all grades) across all cohorts were peripheral edema, nausea, vomiting, increased blood creatinine, dyspnea, fatigue, and decreased appetite.Adverse ReactionsPredominantly Grade 3 or 4. (Bioon.com)