Excerpt:TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.
Title:
Novartis receives European Commission approval for Tabrecta for the treatment of METex14 skipping advanced non-small cell lung cancer
Excerpt:Novartis announced today that the European Commission (EC) approved Tabrecta (capmatinib) as a monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
Title:
Health Canada approves (Pr)Tabrecta®: Targeted cancer therapy for locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations
Excerpt:Novartis Pharmaceuticals Canada Inc. (Novartis) is pleased to announce that Health Canada has granted a Notice of Compliance with conditions (NOC/c) for Tabrecta® (capmatinib tablets) for the treatment of adult patients with locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations....The conditional approval of Tabrecta® is based on results from the pivotal GEOMETRY mono-1 Phase II multi-center, non-randomized, open-label, multi-cohort study.
Title:
Incyte Announces Approval of Tabrecta™ (capmatinib) in Japan for the Treatment of Patients with Advanced Non-Small Cell Lung Cancer with METex14
Excerpt:Incyte (Nasdaq: INCY) today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved Tabrecta™ (capmatinib) for MET exon 14 skipping (METex14) mutation-positive advanced and/or recurrent unresectable non-small cell lung cancer (NSCLC)....Tabrecta is the third Incyte-discovered medicine to receive approval in Japan.
Evidence Level:Sensitive: A2 - Guideline
Excerpt:The NCCN NSCLC Panel also preference stratified regimens that are recommended for METex14 skipping mutations and voted that capmatinib is a preferred first-line therapy...
Evidence Level:Sensitive: B - Late Trials
Title:
1391P - Capmatinib vs docetaxel as second- or third-line (2/3L) therapy in patients (pts) with METex14-mutated advanced NSCLC (aNSCLC): The GeoMETry-III trial
Excerpt:Eligible pts included EGFR wild type, ALK rearrangement−negative, stage IIIB/IIIC or IV METex14–mutated NSCLC who have progressed on 1/2L of systemic therapy….Of 15 pts in cap arm, 8 had partial response (53.3%, 95% CI 26.6-78.7) vs none in doc arm (95% CI 0-41.0). Disease control rate was 73.3%; 95% CI 44.9-92.2 vs 57.1%; 95% CI 18.4-90.1, respectively....Overall, the numerical differences in PFS and ORR showed trends favoring cap, and together with safety, are consistent with previous results of the pivotal GeoMETry mono-1 study.
Evidence Level:Sensitive: B - Late Trials
Title:
Novartis announces MET inhibitor capmatinib (INC280), the first potential treatment for METex14 mutated advanced non-small cell lung cancer, granted priority FDA review
Excerpt:Novartis announced today that the US Food and Drug Administration (FDA) accepted and granted Priority Review to capmatinib’s (INC280) New Drug Application (NDA). Capmatinib is a MET inhibitor being evaluated as a treatment for first-line and previously treated patients with locally advanced or metastatic MET exon 14 skipping (METex14) mutated non-small cell lung cancer (NSCLC).
Evidence Level:Sensitive: B - Late Trials
Title:
Novartis investigational lung cancer therapy capmatinib (INC280) granted FDA Breakthrough Therapy Designation for patients with MET-mutated advanced non-small cell lung cancer
Excerpt:Novartis announced that the U.S. Food and Drug Administration granted Breakthrough Therapy Designation to capmatinib (INC280) as a first-line treatment for patients with metastatic MET exon14 skipping-mutated non-small cell lung cancer (NSCLC).
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
Special Drug Use-results Surveillance of Tabrecta Tablets
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC
More C2 evidence
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
Real-World Assessment of Clinical Outcomes in Metastatic NSCLC Patients With MET Exon 14 Skipping Mutation and Brain Metastases Treated With Capmatinib
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
Study of Capmatinib in Indian Patients With MET Exon 14 Skipping Mutation Positive Advanced NSCLC.
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
Treatment Plan CINC280A02001M to Provide Access to Capmatinib, for MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC)
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor
Evidence Level:Sensitive: C2 – Inclusion Criteria
Title:
Capmatinib in Patients With Non-small Cell Lung Cancer Harboring cMET exon14 Skipping Mutation
Less C2 evidence
Evidence Level:Sensitive: C3 – Early Trials
Title:
1383P - Efficacy of capmatinib compared to standard of care for German patients with locally advanced or metastatic NSCLC harboring METex14 mutations: Results from the RECAP study
Excerpt:The RECAP study provided comparative evidence of capmatinib vs standard of care (SoC) in first (1L) and second line (2L) NSCLC pts with METex14 mutations (NCT05796726)….For 1L pts, the naive comparison showed a significant benefit of capmatinib for OS (median 25.49 vs 14.59 months; HR 0.58; 95% CI 0.39-0.87; p=0.011), PFS (median 12.45 vs 5.03 months; HR 0.44; 95% CI 0.31-0.63; p<0.001) and ORR (event rate 68.3 vs 26.9%; RR 2.54; 95% CI 1.80-3.58; p<0.001).
Evidence Level:Sensitive: C3 – Early Trials
Title:
Real-world assessment of treatment effectiveness in patients with advanced non-small cell lung cancer (aNSCLC) with MET exon 14 skipping (METex14).
Excerpt:Pts who received 1L capmatinib had higher rwORR and longer rwPFS, OS, and TTD than pts who received 1L IO mono or CT alone or in combination...Our analysis suggests that capmatinib in aNSCLC with METex14 yields numerically better clinical outcomes than IO or CT alone or in combination.
DOI:10.1200/JCO.2023.41.16_suppl.e21112
Evidence Level:Sensitive: C3 – Early Trials
Title:
Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib
Excerpt:To assess real-world clinical outcomes in patients with non-small-cell lung cancer with MET exon 14 skipping mutation and brain metastases (BM) who received capmatinib....In patients treated with first-line (1L) capmatinib (n = 55), the rwORR was 90.9% systemically and 87.3% intracranially; median systemic rwPFS was 14.1 months. Among radiation-naive patients on 1L capmatinib (n = 20), rwORR was 85.0%, both systemically and intracranially; median systemic rwPFS was 14.1 months....This study showed substantial systemic and intracranial effectiveness for capmatinib in real-world setting; findings were consistent for RT-naive patients.
DOI:10.2217/fon-2022-1133
Evidence Level:Sensitive: C3 – Early Trials
Title:
388P - Capmatinib in Chinese adults with EGFR wt, ALK rearrangement negative (ALK-R−), MET exon 14 skipping mutation (METex14), advanced NSCLC: Results from the phase II GEOMETRY-C study
Excerpt:...stage IIIB/IIIC/IV, METex14 NSCLC received capmatinib 400 mg twice daily….This primary analysis based on ORR shows that capmatinib delivers a high response rate and manageable safety profile in Chinese pts.
Evidence Level:Sensitive: C3 – Early Trials
Title:
1106P - Capmatinib for METex14 non-small cell lung cancer patients: Results of the real-world study IFCT-2104 CapmATU
Excerpt:160 pts received capmatinib and 146 had a METex14 NSCLC and were included in the analysis….Best objective response rate (ORR) was 55.2% [95% CI 46.8-63.6]. For pts treated in 1st, 2nd and ≥3rd line, median PFS was 7.7 m [95% CI 4.0-NR], 6.0 m [95% CI 3.6-7.7], 4.1 m [95% CI 2.5-5.1], respectively....For pts with and without brain metastases, median PFS was 3.0 m [95% CI 2.4-5.8] and 5.3 m [95% CI 4.5-7.7]; best ORR was 47.6% [95% CI 32.5 - 62.7] and 58.7% [95% CI 48.6 - 68.8], respectively....This RW study confirms effectiveness of capmatinib in METex14 NSCLC pts, including those who have been pretreated, with poor PS or brain metastases.
Evidence Level:Sensitive: C3 – Early Trials
Title:
EP08.02-122 Real-world Experience with Capmatinib in MET Exon 14-mutated Non-small Cell Lung Cancer (RECAP)
Excerpt:Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed….For all patients the objective response rate (ORR) to capmatinib was 58% (95% CI, 47-69), while it was 68% (95% CI, 50-82) in treatment-naïve and 50% (95% CI, 35-65) in pretreated patients....In patients with MET exon 14 skipping mutation, capmatinib shows durable systemic and intracranial efficacy and a manageable safety profile.
Evidence Level:Sensitive: C3 – Early Trials
Title:
Real-world assessment of clinical outcomes in NSCLC patients with MET exon 14 skipping mutation and brain metastases (BM) treated with capmatinib.
Excerpt:The current study examined real-world clinical outcomes of pts with NSCLC with MET exon 14 skipping mutation and BM who were treated with capmatinib, including those who were RT-naïve....In the overall cohort, the IC rwORR was 87.3% (rwDCR 96.4%) for capmatinib 1L and 27.3% (rwDCR 45.5%) for IO 1L. Median systemic rwPFS was 14.1 months for capmatinib 1L and 5.1 months for IO 1L....This study shows a substantial systemic and IC effectiveness associated with capmatinib 1L use in pts with NSCLC with MET exon 14 and BM in the real-world setting.
DOI:10.1200/JCO.2022.40.16_suppl.e21171
Evidence Level:Sensitive: C3 – Early Trials
Title:
Novartis receives positive CHMP opinion for Tabrecta® for patients with METex14 advanced non-small cell lung cancer
Excerpt:Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion and recommended granting marketing authorization of Tabrecta® (capmatinib) as a monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy....The CHMP opinion is based on results from the Phase II GEOMETRY mono-1 trial that demonstrated positive overall response rates (ORR) among adult patients with advanced NSCLC whose tumors had alterations leading to METex14 skipping...
Evidence Level:Sensitive: C3 – Early Trials
Title:
Capmatinib in treatment (Tx)-naive MET exon 14-mutated (METex14) advanced non-small cell lung Cancer (aNSCLC): Updated results from GEOMETRY mono-1
Excerpt:In Cohort 7, 32 Tx-naive pts received capmatinib 400 mg twice daily. ORR was68.8% (95% CI, 50.0-83.9), with mDOR of 16.59 months (95% CI, 8.34-not estimable[NE]). mPFS was 12.45 months (95% CI, 6.87-20.50) and mOS was not reached yet. Primary efficacy analysis for Cohort 7 confirms previousfindings fromCohort 5b in Tx-naive pts with METex14, showing an ORR ofw70% and mPFS of>1year. Safety data are consistent with previously published data for all pts. These datacontinue to support the use of capmatinib for 1L Tx of pts with METex14 aNSCLC.
Evidence Level:Sensitive: C3 – Early Trials
Title:
MET-Targeted Therapies and Clinical Outcomes: A Systematic Literature Review
Excerpt:...a phase II study (GEOMETRY mono-1 study) involving patients with NSCLC harboring MET exon 14 skipping mutations who were assigned to cohorts according to previous lines of therapy. The authors reported that patients with NSCLC with a MET exon 14 skipping mutation who had already received one or two lines of therapy receiving capmatinib 400 mg tablet twice daily (BID) exhibited an overall response of 41% (28/69) and a mPFS of 5.2 months. Treatment-naïve patients exhibited an overall response and PFS of 68% (19/28) and 12.4 months, respectively (Table 2).
DOI:10.1007/s40291-021-00568-w
Evidence Level:Sensitive: C3 – Early Trials
Title:
Role of capmatinib in MET exon 14-mutated advanced non-small cell lung cancer (NSCLC): A systematic review.
Excerpt:...evaluating the clinical response of capmatinib in MET ex14 mutated advanced NSCLC....phase 2 study showed an overall response rate (ORR) of 41% (69/97; 95% CI, 29-53) with 41% partial response (PR), and 36% stable disease (SD)...Our results showed that capmatinib has promising anti-tumor activity in patients with NSCLC harboring MET exon 14 skipping mutation.
DOI:10.1200/JCO.2021.39.15_suppl.e21150
Evidence Level:Sensitive: C3 – Early Trials
Title:
Capmatinib in MET exon 14-mutated, advanced NSCLC: Updated results from the GEOMETRY mono-1 study
Excerpt:160 pts with METex14 who received capmatinib 400 mg BID were analyzed. ORR of 65.6% (95% CI 46.8-81.4) for the treatment-naive expansion Cohort 7 was in line with that previously reported for Cohort 5b….Results of Cohort 7 confirm those previously reported for Cohort 5b showing higher efficacy of capmatinib when used as 1L in METex14 NSCLC pts. A clinically meaningful median OS of 20.8 mo in 1L (Cohort 5b) and of 13.6 mo in relapse (Cohort 4) was also observed and, together with the continued manageable toxicity profile, the data support capmatinib as a valuable targeted treatment option for METex14 NSCLC pts.
DOI:10.1200/JCO.2021.39.15_suppl.9020
Evidence Level:Sensitive: C3 – Early Trials
Title:
A Phase II Study of Capmatinib in Patients with MET-Altered Lung Cancer Previously Treated with a MET Inhibitor
Excerpt:Patients with advanced NSCLC harboring MET amplification or MET exon 14 skipping received capmatinib 400 mg twice daily...Overall, the median PFS and OS were 5.5 (95% CI 1.3-11.0) and 11.3 (95% CI 5.5-not reached) months...
DOI:10.1016/j.jtho.2021.01.1605
Evidence Level:Sensitive: C3 – Early Trials
Title:
The Clinical Impact of Capmatinib in the Treatment of Advanced Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification
Excerpt:A total of 72 patients were included in this analysis (Group A: GCN ≥ 10 or METex14, n=14; Group B: others, n=58)….within Group A, median OS was 21.5 months (95% CI, 20.8 - NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 - NA) for capmatinib-untreated patients (p=0.025).
DOI:10.4143/crt.2020.1331
Evidence Level:Sensitive: C3 – Early Trials
Title:
Capmatinib in Japanese patients with MET exon 14 skipping-mutated or MET-amplified advanced NSCLC: GEOMETRY mono-1 study
Excerpt:Among METΔex14-mutated patients, in the 1L group, one patient achieved partial response (DOR of 4.24 months) and the other had stable disease. In the 2/3L group, the ORR was 36.4% (95% CI 10.9%-69.2%), median DOR was not evaluable, and progression-free survival was 4.70 months.
Evidence Level:Sensitive: C3 – Early Trials
Title:
P85.04 - Capmatinib in Patients with METex14-Mutated Non-Small Cell Lung Cancer: GEOMETRY Mono-1 Asian Subgroup Analysis
Excerpt:Overall response rate among patients with METex14-mutated NSCLC regardless of line of therapy in Asian and non-Asian subgroup was 45% (95% CI: 23.1, 68.5) and 49.4% (95% CI: 37.8, 61.0), respectively...Capmatinib demonstrated clinically meaningful efficacy and manageable safety profile in Asian patients with METex14-mutated NSCLC...
Evidence Level:Sensitive: C3 – Early Trials
Title:
Phase 2 GEOMETRY Mono-1 Study: Capmatinib in Patients with METex14-mutated Advanced Non-Small Cell Lung Cancer who Received Prior Immunotherapy
Excerpt:Cohort 4 (pre-treated METex14 NSCLC) is included in this analysis…Median PFS on prior IO was 3.29 months (95%CI 2.10-5.16). Efficacy of capmatinib was demonstrated in patients who received and who did not receive prior IO: ORR 57.9% (n=11/19; 95%CI 33.5-79.7) and 34% (n=17/50; 95%CI 21.2-48.8)…
Evidence Level:Sensitive: C3 – Early Trials
Title:
1285P - Capmatinib in patients with METex14-mutated advanced non-small cell lung cancer who received prior immunotherapy: The phase II GEOMETRY mono-1 study
Excerpt:...69 pts with METex14 NSCLC were enrolled...Efficacy of capmatinib was demonstrated in pts who received and who did not receive prior IO: ORR 57.9% (n=11/19; 95%CI 33.5-79.7) and 34% (n=17/50; 95%CI 21.2-48.8); median DOR 11.20 months (95%CI 3.35-NE) and 7.16 months (95%CI 4.17-11.14), respectively.
Evidence Level:Sensitive: C3 – Early Trials
Title:
Capmatinib in patients with METex14-mutated or high-level MET-amplified advanced non–small-cell lung cancer (NSCLC): results from cohort 6 of the phase 2 GEOMETRY mono-1 study.
Excerpt:In METex14-mutated NSCLC pts, per BIRC assessment: ORR was 48.4%, median DOR was 6.93 months (mo, not yet mature, 95% CI: 4.17–NE) and median PFS was 8.11 mo (not yet mature, 95% CI: 4.17–9.86)….Capmatinib was confirmed to be efficacious in 2nd line, METex14-mutated NSCLC pts.
DOI:10.1200/JCO.2020.38.15_suppl.9520
Evidence Level:Sensitive: C3 – Early Trials
Title:
Abstract CT082: Capmatinib in METex14-mutated (mut) advanced non-small cell lung cancer (NSCLC): Results from the phase II GEOMETRY mono-1 study, including efficacy in patients (pts) with brain metastases (BM)
Excerpt:BIRC neuro-radiologist review of 13 pts with evaluable baseline BM suggested that capmatinib has anti-tumor efficacy in the brain. Capmatinib also showed deep and durable responses in pts with METex14-mut advanced NSCLC regardless of line of therapy and demonstrated a manageable safety profile.
DOI:10.1158/1538-7445.AM2020-CT082
Evidence Level:Sensitive: C3 – Early Trials
Title:
Capmatinib in MET Exon 14–Mutated or MET-Amplified Non–Small-Cell Lung Cancer
Excerpt:We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC….Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients...the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively....Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously.
DOI:10.1056/NEJMoa2002787
Evidence Level:Sensitive: C4 – Case Studies
Title:
Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors
Excerpt:An 82-year-old female, with a 25 pack-year smoking history, was diagnosed with stage IV large cell lung carcinoma with right hilar node metastases…Comprehensive genomic profiling was performed on the primary resection and demonstrated that the tumor harbored a METex14 alteration (c.3028G>C) and TP53 p.N30fs*14...The patient was treated with capmatinib for more than 5 months and had a tumor reduction of 53%, a partial response (Fig. 5A and B).
DOI:10.1158/2159-8290.CD-15-0285
Evidence Level:Sensitive: D – Preclinical
Title:
MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer
Excerpt:In vitro clonogenic survival assays demonstrated radiosensitization with capmatinib in both MET exon 14-mutated and MET-amplified NSCLC cell lines.
DOI:https://doi.org/10.1016/j.ijrobp.2023.11.013