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.

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.

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.

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.

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...

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.

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).

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).

......

......

......

......

......

......

......

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).

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.

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.

...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.

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.

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.

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.

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...

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.

...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).

...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.

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.

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...

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).

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. 

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)…

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...

...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.

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.

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.

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.

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).

In vitro clonogenic survival assays demonstrated radiosensitization with capmatinib in both MET exon 14-mutated and MET-amplified NSCLC cell lines.