dm+d

Unassigned

New Medicines

Tabrecta Stage III or IV, EGFR wild-type, cMET amplified or cMET mutation non-small cell lung cancer (NSCLC)

Information

Tabrecta
New molecular entity
Novartis
Novartis

Development and Regulatory status

Phase II Clinical Trials
Pre-registration (Filed)
Launched
Jun 21Filed in EU via centralised procedure; assume for this indication [16].
Jan 21EU filing planned for H1 21 [15].
Aug 20Tablecta® tablets 150mg and 200mg as a treatment for unresectable advanced/recurrent NSCLC with MET gene exon 14 skipping mutation positive launched in the US [13].
Jun 20Novartis is now planning an EU filing, using the centralised procedure, for treatment-naïve EGFR wild-type, cMET amplified or cMET mutation positive NSCLC, stage IIIB or IV (any histology) [12].
May 20Approved in US under Accelerated Approval process, therefore continued approval may require confirmatory trial data. The licensed indication is "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." No previous treatment is specified [10]. Launch is expected mid-May with an expected cost around $18k for 28 days supply [11].
Feb 20FDA grant priority review for capmatinib based on PII data from the GEOMETRY mono-1 trial in 1st-line & previously treated pts with METex14 mutated advanced NSCLC. [9]
Dec 19Novartis decided to discontinue EU development for capmatinib in June 18 [8].
Jun 19Breakthrough Therapy Designation for this indication in US.[7]
Dec 18Filings planned for 2019 [5].
Dec 17In PIII development. Planned filing date for the lead indication of NSCLC is 2019 [2].

Category

A small-molecule proto-oncogene protein first-in-class c-Met inhibitor. c-Met over-expression has also been associated with resistance to EGFR inhibitors.
Around 72% of lung cancers are non-small-cell lung cancers. Most lung cancers are diagnosed in the later stages, with 21% of people presenting with locally and regionally advanced disease (stage IIIB) and 48% presenting with metastatic disease (stage IV) [1].
Stage III or IV, EGFR wild-type, cMET amplified or cMET mutation non-small cell lung cancer (NSCLC)
Oral

Trial or other data

Oct 18Preliminary efficacy data from PII GEOMETRY mono-1 trial (NCT02414139) evaluating capmatinib in 94 adult patients with advanced NSCLC harboring MET exon-14 skipping mutations showed overall response rate (ORR) of 72.0% (95% CI: 50.6-87.9) and 39.1% (95% CI: 27.6-51.6) in treatment-naive patients and previously treated patients respectively. The most common treatment-related AEs included peripheral edema, nausea, vomiting, and increased blood creatinine levels. Of patients treated with INC280, 83.8% experienced an AE, with 33.1% having grade 3/4 AEs [6].
Oct 18PII trial (NCT02414139) still recruiting; collection of primary outcome data now expected to complete May 21 [3].
Feb 18NCT02414139 still recruiting; timescales unchanged [3].
Jun 15PII trial to evaluate capmatinib in patients with EGFR wild-type, advanced NSCLC who have received systemic therapy for advance/metastatic cancer starts (NCT02414139). 318 patients will be enrolled globally including in the US & EU (plus UK). Primary outcome is overall response rate and collection of these data are due to complete Sep 18 [3].

Evidence based evaluations