dm+d

40268611000001109

New Medicines

TepmetkoAdvanced non-small cell lung cancer (NSCLC) with mesenchymal–epithelial transition (MET) exon 14 skipping mutations or MET amplification - second-line

Information

Tepmetko
New molecular entity
Merck (or Merck KGaA)
Merck (or Merck KGaA)

Development and Regulatory status

Launched
Approved (Licensed)
Approved (Licensed)
September 2021
Yes
Apr 22UK price for 225mg tablet, 60=£7200.00 [18]
Feb 22Approved by the EU [17].
Dec 21Recommended for EU approval by CHMP “as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.” Tepmetko will be available as 225 mg film-coated tablets [16].
Oct 21Tepotinib was licensed in the UK on 24 September and has been available to use since then [14,15].
Oct 21The indication approved by the MHRA is treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations [14].
Oct 21MHRA approves tepotinib for advanced non-small cell lung cancer with METex14 skipping, via the FDA project ORBIS [13].
Jul 21MHRA grants EAMS status to Merck Serono for tepotinib in the treatment of NSCLC that has certain abnormal changes in the mesenchymal-epithelial transition factor gene (MET) and which has spread and/or cannot be removed by surgery [12].
Feb 21Tepmetko will bear a list price of $20,898.60 in the US for a 30-day supply. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [10].
Feb 21Approved in US [9]
Nov 20EMA validates for review, NDA for tepotinib for treatment of adult patients with advanced NSCLC harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations [6].
Aug 20Accepted for priority review in US [5]
Sep 19US FDA grant breakthrough therapy design, on basis of data from ongoing VISION study (n=73), which has reported overall objective response rate in region of 50.0% [3].

Category

A small-molecule inhibitor of proto-oncogene protein c-met. Tepotinib inhibits both hepatocyte growth factor-dependent and -independent c-Met activation in low nanomolar concentrations
MET-mutations are clinically unique molecular subtypes of NSCLC, with MET exon 14 (METex14) alteration conferring oncogene addiction in ~3-4% of NSCLC. There are currently no approved therapies specifically targeting METex14 and/or c-Met amplification [1].
Advanced non-small cell lung cancer (NSCLC) with mesenchymal–epithelial transition (MET) exon 14 skipping mutations or MET amplification - second-line
Oral

Further information

Yes

Trial or other data

Dec 20PII VISION study continues to recruit [7].
Sep 20Updated results from the PII announced. Overall objective response rate (ORR) in evaluable patients (n=146; 95 L+ and 84 T+) was 44.5% (95% CI: 36.3, 53.0) by Independent Review Committee (IRC), and 54.8% (95% CI: 46.4, 63.0) by investigator-assessed (INV). ORR was consistent across subgroups, supporting robustness of efficacy. ORR in liquid biopsy (L+) was 47.4% (95%CI: 37.0, 57.9) and 54.7% (95% CI: 44.2, 65.0) and in tissue biopsy (T+) was 45.2% (95% CI: 34.3, 56.5) and 58.3% (95% CI: 47.1, 69.0), as assessed by IRC and INV, respectively. Median duration of response (DOR) in L+ patients was 9.9 months (95% CI: 7.2, not estimable [ne]) by IRC and 14.0 months (95% CI: 7.2, ne) by INV, and in T+ pts was 12.4 months (95% CI: 9.7, ne) by IRC and 16.4 months (95% CI: 9.7, ne) by INV. Median progression free survival (mPFS) in L+ patients was 8.5 months (6.7, 10.9) by IRC and 8.5 months (5.8, 11.0) by INV, and in T+ patients was 11.0 months (7.8, 17.1) by IRC and 12.2 months (6.8, 19.6) by INV. ORR of patients in cohort A was 57.1% (95% CI: 28.9, 82.3) as assess by IRC and 53.8% (95% CI: 25.1, 80.8) as assessed by INV. Partial response was seen in eight and seven patients assessed by IRC and INC respectively. Stable disease was observed in three patients each assessed by IRC and INC [8].
Dec 19PII VISION study is recruiting; collection of primary outcome data is due to complete Dec 21 [4].
Nov 18PII VISION study is recruiting [2].
Sep 16PII VISION trial to assess the efficacy of tepotinib as a second-line treatment in patients with stage IIIB/IV non-small cell lung cancer, with MET exon 14 skipping alterations starts (NCT02864992). The open-label trial intends to enrol approximately 120 patients in Spain, Belgium, France, Germany, Italy, Poland, Japan and the US. Collection of primary outcome data (objective response) is due to complete Jun 19 [2].

Evidence based evaluations