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DRUG:

Tepmetko (tepotinib)

i
Other names: MSC2156119J, EMD1214063, EMD-1214063, MSC-2156119J, MSC 2156119, MSC 2156119J, MSC-2156119, MSC2156119, EMD 1214063
Company:
EMD Serono
Drug class:
c-MET inhibitor
Related drugs:
20d
Tepotinib in Cholangiocarcinoma with MET Amplification: A Case Report. (PubMed, Onco Targets Ther)
Systemic therapy, such as chemotherapy using gemcitabine and cisplatin, is the first choice for patients with cholangiocarcinoma who were inoperable. The development of precision medicine has expanded the paradigm of targeted therapies to increasingly favorable options in the second line and beyond, and prolong overall survival. Detecting druggable mutations (mutations potentially amenable to treatment with) for identifying a landscape of therapeutic options is imperative for managing cholangiocarcinoma.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification
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cisplatin • gemcitabine • Tepmetko (tepotinib)
1m
Asia-inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler. (PubMed, Clin Transl Sci)
Herein, we describe recent case examples of model-informed Asia-inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3-related inhibitors, tuvusertib and berzosertib (oncology), the toll-like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal-epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease). Through these case studies, we illustrate pragmatic approaches to ethnic sensitivity assessments and the application of a model-informed drug development toolkit including population pharmacokinetic/pharmacodynamic modeling and pharmacometric disease progression modeling and simulation to enable early conduct of Asia-inclusive MRCTs. These examples demonstrate the value of a Totality of Evidence approach where every patient's data matter for de-risking ethnic sensitivity to inter-population variations in drug- and disease-related intrinsic and extrinsic factors, enabling inclusive global development strategies and timely evidence generation for characterizing benefit/risk of the proposed dosage in Asian populations.
Review • Journal
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ATR (Ataxia telangiectasia and Rad3-related protein)
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Tepmetko (tepotinib) • berzosertib (M6620) • cladribine • tuvusertib (M1774)
2ms
A Master Protocol to Evaluate Biomarker-Driven Therapies and Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP Screening Study) (SWOG-Fall 2024)
Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC. S1900J (MET amplification) is opening fall 2024 and is studying amivantamab in NSCLC...One hundred seventy-four (5%) were submitted with the classification of "Other". The most common reasons included: no sub-studies available, patient chose hospice, and patient transferred to different hospital.
Clinical • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion
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FoundationOne® CDx
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Tagrisso (osimertinib) • Lumakras (sotorasib) • Cyramza (ramucirumab) • Rybrevant (amivantamab-vmjw) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
2ms
Spatial profiling of METex14-altered NSCLC under tepotinib treatment: Shifting the immunosuppressive landscape. (PubMed, Neoplasia)
Our study supports the integration of genetic profiling into the management of early and locally advanced NSCLC to guide personalized, targeted interventions. These findings underscore the need to further evaluate combinations of MET inhibitors and immunotherapies.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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Tepmetko (tepotinib)
2ms
Exceptional sustained long-term complete response to Tepotinib in a MET-amplified advanced intrahepatic biliary tract cancer failing Durvalumab plus Cisplatin and Gemcitabine. (PubMed, Oncologist)
Tepotinib showed remarkable efficacy in treating MET-amplified intrahepatic cholangiocarcinoma, underscoring the importance of molecular profiling in BTCs and suggesting a potential new therapeutic approach for this rare cancer subtype.
Journal • PD(L)-1 Biomarker • Metastases
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TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
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TP53 mutation • MET amplification • MET mutation
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cisplatin • Imfinzi (durvalumab) • gemcitabine • Tepmetko (tepotinib)
2ms
Enrollment open
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • RET rearrangement
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Cyramza (ramucirumab) • Tepmetko (tepotinib)
2ms
Enhancing Retinoic Acid-mediated Effects Through Inhibition of CYP26A1, CYP26B1 and HGF Signaling in Neuroblastoma Cells. (PubMed, Anticancer Res)
Independent of MYCN amplification, inhibitors of RA metabolism or HGF signaling might prevent the emergence of RA-resistant neuroblastoma cells when co-applied with RA.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CYP26A1 (Cytochrome P450 Family 26 Subfamily A Member 1)
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MYCN amplification
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Tepmetko (tepotinib)
2ms
Remarkable pathological response to neoadjuvant tepotinib in lung adenocarcinoma with MET exon 14 skipping mutation: A case report. (PubMed, Thorac Cancer)
After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Postoperative tepotinib continued, with no relapse at 6-month follow-up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping-mutated NSCLC, warranting further clinical trials.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET exon 14 mutation
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Orpathys (savolitinib) • Tepmetko (tepotinib)
3ms
An observational study on the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma. (PubMed, Discov Oncol)
The EGFR mutation, ALK fusion gene, and MET exon 14 skipping mutation were detected in patients with pulmonary sarcomatoid carcinoma in clinical practice, and some patients achieved long survival times after receiving targeted therapy. Further investigation is necessary to evaluate the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma.
Observational data • Journal
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation • BRAF mutation • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • ALK-ROS1 fusion
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Xalkori (crizotinib) • gefitinib • Tepmetko (tepotinib)
3ms
MET exon 14 skipping mutations in non-small-cell lung cancer: real-world data from the Italian biomarker ATLAS database. (PubMed, ESMO Open)
Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with METex14. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. Their activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the management of patients with METex14.
Journal • Real-world evidence • Real-world
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MET (MET proto-oncogene, receptor tyrosine kinase)
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Tepmetko (tepotinib) • Tabrecta (capmatinib)
3ms
A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17). (PubMed, ESMO Open)
Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.
Clinical • P2 data • Journal • Metastases
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MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tepmetko (tepotinib)
3ms
Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov)
P2, N=337, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Feb 2025 --> Oct 2025
Trial completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tepmetko (tepotinib)
4ms
Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. (PubMed, Lancet Oncol)
Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated.
P2 data • Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tagrisso (osimertinib) • Tepmetko (tepotinib)
4ms
A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2) (clinicaltrials.gov)
P2, N=140, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: May 2024 --> Oct 2025
Trial completion date • Metastases
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tagrisso (osimertinib) • Tepmetko (tepotinib)
4ms
Case report: Response to tepotinib in Chinese non-small cell lung cancer patients harboring METex14 skipping with varying features. (PubMed, Front Oncol)
One patient has concomitant BRAF V600E mutation, and another patient had savolitinib as first line of therapy but discontinued due to hepatotoxicity. Our experience showed in real clinical setting, tepotinib had robust and durable clinical activity and a favorable toxicity profile in Chinese patients with METex14 skipping NSCLC. It is the first report on the effectiveness of tepotinib in a patient with both METex14 skipping and BRAF V600E mutations and successful MET inhibitor switch after MET inhibitor-induced liver injury.
Journal
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BRAF (B-raf proto-oncogene)
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Orpathys (savolitinib) • Tepmetko (tepotinib)
5ms
Journal • Metastases
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tepmetko (tepotinib)
5ms
Discovery of Potent and Selective c-Met Degraders for Hepatocellular Carcinoma Treatment. (PubMed, J Med Chem)
Importantly, H11 also demonstrated more potent inhibitory activity against Ba/F3-TPR-MET-D1228N and Ba/F3-TPR-MET-Y1230H cell lines than did tepotinib. In summary, H11 displayed potent anti-HCC activity as a degrader and may overcome resistance to type Ib inhibitors, making it a new therapeutic strategy for HCC with MET alterations.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tepmetko (tepotinib)
5ms
Mesenchymal-epithelial transition factor exon 14 skipping mutation-positive granulocyte colony-stimulating factor-producing lung adenocarcinoma mimicking lung abscess: A case report. (PubMed, Respirol Case Rep)
G-CSF-producing lung tumours can present imaging findings that mimic lung abscesses. Tepotinib therapy may be effective for patients with MET exon 14 skipping mutation, including those with G-CSF-producing lung cancer.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tepmetko (tepotinib)
5ms
PhI/II Study of Amivantamab and Tepotinib Combo in MET-altered Non-small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=60, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting
Enrollment open
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
Rybrevant (amivantamab-vmjw) • Tepmetko (tepotinib)
5ms
KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination. (PubMed, Cell Commun Signal)
We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • HGF (Hepatocyte growth factor) • ENO1 (Enolase 1)
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Mekinist (trametinib) • Lumakras (sotorasib) • Tepmetko (tepotinib) • omeprazole
6ms
A novel HLA-DQB2::MET gene fusion variant in lung adenocarcinoma with prolonged response to tepotinib: a case report. (PubMed, Transl Lung Cancer Res)
A 73-year-old female was initially started on carboplatin, pemetrexed and pembrolizumab with maintenance, but eventually had progression in the left upper lobe (LUL). The patient's response to a MET inhibitor, tepotinib, underscores the potential efficacy of selective MET inhibitors for individuals with previously unexplored MET fusions. The positive response to tepotinib of a patient with NSCLC harboring a novel MET-Fusion underscores the importance of the use of comprehensive next-generational sequencing-based panels and highlights the necessity for additional research and clinical exploration of selective MET inhibitors for managing NSCLC with MET rearrangements.
Journal • PD(L)-1 Biomarker • IO biomarker
|
MET (MET proto-oncogene, receptor tyrosine kinase) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ Beta 2)
|
Keytruda (pembrolizumab) • carboplatin • pemetrexed • Tepmetko (tepotinib)
6ms
Brief Report: Tepotinib as a Treatment Option in MET Exon 14 Skipping-Positive Lung Cancers-Investigating Discordance Between ArcherMET and the Oncomine Dx Target Test. (PubMed, JTO Clin Res Rep)
Our findings suggest that tepotinib has comparable therapeutic effects in patients with METex14 skipping-positive NSCLC irrespective of the concordance of results between ODxTT and ArcherMET. Tepotinib is a possible treatment option for patients with METex14 skipping, even in patients with discordant test results.
Journal • Discordant
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MET (MET proto-oncogene, receptor tyrosine kinase)
|
Oncomine™ Dx Target Test • ArcherMET
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Tepmetko (tepotinib)
6ms
Prolonged complete response to adjuvant tepotinib in a patient with newly diagnosed disseminated glioblastoma harboring mesenchymal-epithelial transition fusion. (PubMed, Oncologist)
Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.
Journal
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PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
|
Tepmetko (tepotinib)
6ms
Phase 2 trial of crizotinib in Japanese patients with advanced NSCLC harboring a MET gene alteration: a Co-MET study. (PubMed, Int J Clin Oncol)
Crizotinib showed a clinical activity similar to that of tepotinib and capmatinib in patients with NSCLC harboring MET exon 14 skipping mutations.
P2 data • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • MET exon 14 mutation
|
Xalkori (crizotinib) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
7ms
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET exon 14 mutation
|
Tepmetko (tepotinib) • Tabrecta (capmatinib)
7ms
ctDNA as a biomarker in phase II study of tepotinib in advanced solid cancers with MET exon 14 skipping mutation or amplification (KCSG AL19-17). (ASCO 2024)
In the liquid biomarker analysis in the MET-dysregulated cancer patients who were treated with tepotinib, the presence of ctDNA METalteration at baseline was associated with a higher response rate but shorter PFS and OS. The molecular response was well correlated with the radiological response and associated with better outcomes. (Funded by Merck KGaA, Darmstadt, Germany, ClinicalTrials.gov number, NCT04647838.)
P2 data • Circulating tumor DNA • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
AlphaLiquid® 100
|
Tepmetko (tepotinib)
7ms
A Phase 1a/1b Study to Determine the Recommended Phase 2 Dose, of Tepotinib in Participants With MET Alterations and Brain Tumors (clinicaltrials.gov)
P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=60 --> 0 | Trial completion date: Dec 2025 --> Apr 2024 | Active, not recruiting --> Withdrawn | Trial primary completion date: Dec 2025 --> Apr 2024
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET exon 14 mutation • IDH wild-type
|
Tagrisso (osimertinib) • Tepmetko (tepotinib)
7ms
Targeted therapeutic options in early and metastatic NSCLC-overview. (PubMed, Pathol Oncol Res)
Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation...Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1...Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.
Review • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
|
BRAF V600E • KRAS mutation • EGFR mutation • PD-L1 overexpression • KRAS G12C • BRAF V600 • EGFR T790M • RET fusion • EGFR exon 20 insertion • EGFR expression • EGFR overexpression • MET exon 14 mutation • RET mutation • ROS1 fusion • EGFR exon 20 mutation
|
Keytruda (pembrolizumab) • Tagrisso (osimertinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Lumakras (sotorasib) • Krazati (adagrasib) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
8ms
Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION. (PubMed, Br J Cancer)
Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian patients with METex14 skipping NSCLC.
Journal • Metastases
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET exon 14 mutation
|
Tepmetko (tepotinib)
8ms
A Master Protocol to Evaluate Biomarker-Driven Therapies and Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP Screening Study) (SWOG-Spring 2024)
There are three currently active sub-studies and one soon to be activated sub-study studying amivantamab-vmjw in MET amplification positive NSCLC (S1900J). Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC...One hundred seventy (7%) were submitted with the classification of "Other". The most common reasons included: no sub studies available, patient chose hospice, and patient transferred to different hospital.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion
|
FoundationOne® CDx
|
Tagrisso (osimertinib) • Lumakras (sotorasib) • Cyramza (ramucirumab) • Rybrevant (amivantamab-vmjw) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
8ms
A Phase 1a/1b Study to Determine the Recommended Phase 2 Dose, of Tepotinib in Participants With MET Alterations and Brain Tumors (clinicaltrials.gov)
P1, N=60, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
Enrollment closed • Phase classification • Trial completion date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET exon 14 mutation • IDH wild-type
|
Tagrisso (osimertinib) • Tepmetko (tepotinib)
9ms
MET alterations in advanced non-small cell lung cancer. (PubMed, Curr Probl Cancer)
Capmatinib and tepotinib are currently the only two approved targeted therapies by the U.S. Food and Drug Administration (FDA) for patients with MET exon 14 skipping mutation. Some of these agents are being used in combination with EGFR targeted therapy to mitigate resistance to EGFR inhibitor. These agents are poised to provide new hope for these patients.
Journal • Metastases
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET exon 14 mutation
|
Tepmetko (tepotinib) • Tabrecta (capmatinib)
9ms
Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer. (PubMed, Cancer Lett)
While c-MET inhibitors such as crizotinib, capmatinib, tepotinib and cabozantinib have garnered FDA approval for non-small cell lung cancer (NSCLC), their potential within breast cancer therapy is still undetermined...Furthermore, we highlight the pivotal role of c-MET-targeted therapies in breast cancer, offering a clinical perspective on this promising avenue of intervention. In this pursuit, we strive to unravel the potential of c-MET as a beacon of hope in the fight against breast cancer, unveiling new horizons for therapeutic innovation.
Review • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
Xalkori (crizotinib) • Cabometyx (cabozantinib tablet) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
9ms
Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study. (PubMed, Cancer Sci)
Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION.
P2 data • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET exon 14 mutation
|
Tepmetko (tepotinib)
9ms
Activity of Tepotinib in Hepatocellular Carcinoma With High-Level MET Amplification: Preclinical and Clinical Evidence. (PubMed, JCO Precis Oncol)
High-level METamp may be an oncogenic driver in HCC that is sensitive to MET inhibitors such as tepotinib.
Preclinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression
|
Tepmetko (tepotinib)
9ms
The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC. (PubMed, JTO Clin Res Rep)
Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)-patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)-patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added...The efficacy and safety of combining MET TKIs (crizotinib, capmatinib, or tepotinib) with parent TKIs for acquired MET resistance are efficacious. Radiographic response and AEs did not differ significantly on the basis of the underlying MET TKI used. Loss of MET gene amplification, development of MET on-target mutations, Ras-Raf-MAPK alterations, and EGFR gene amplification were molecular patterns found on progression with dual parent and MET TKI combinations.
Journal • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
TP53 mutation • EGFR mutation • MET amplification • EGFR amplification • MET exon 14 mutation • RAS mutation • MET mutation • MET fusion
|
Xalkori (crizotinib) • pemetrexed • Tepmetko (tepotinib) • Tabrecta (capmatinib)
9ms
Comparison of Tepotinib, Paclitaxel, or Ramucirumab Efficacy According to the Copy Number or Phosphorylation Status of the MET Gene: Doublet Treatment versus Single Agent Treatment. (PubMed, Int J Mol Sci)
These in vitro findings suggest that compared with ramucirumab-plus-paclitaxel, tepotinib-plus-paclitaxel better inhibits the growth of c-MET-positive GC cells, cells lacking MET amplification but containing phosphorylated MET, and cells containing MET mutations. Clinical studies are required to confirm the therapeutic effects of these regimens.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • MET positive
|
paclitaxel • Cyramza (ramucirumab) • Tepmetko (tepotinib)
10ms
Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments. (PubMed, Front Oncol)
Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines...Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.
Review
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
Xalkori (crizotinib) • Tagrisso (osimertinib) • gefitinib • Orpathys (savolitinib) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
10ms
First-line immunotherapy for lung cancer with MET exon 14 skipping and the relevance of TP53 mutations. (PubMed, Eur J Cancer)
CHT-IO is superior to CHT, and IO alone also effective for METΔ14ex NSCLC, especially in the presence of TP53 mutations and independent of PD-L1 expression, but never-smokers are at higher risk of primary PD.
Journal • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PD-L1 expression • TP53 mutation • MET exon 14 mutation
|
Xalkori (crizotinib) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
10ms
A plain language summary of the TROPiCS-02 study in patients with breast cancer (HR-positive/HER2-negative). (PubMed, Future Oncol)
The side effects from sacituzumab govitecan could generally be managed well by doctors. Although there were more side effects with sacituzumab govitecan than with chemotherapy, they were generally mild to moderate.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • PTEN mutation + HR positive
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Tepmetko (tepotinib) • Trodelvy (sacituzumab govitecan-hziy)
12ms
Exploring the interaction of tepotinib with calf thymus DNA using molecular dynamics simulation and multispectroscopic techniques. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc)
Thus, the results of our present investigation offer valuable insights into the interaction between TPT and ctDNA. It is evident that TPT, as an anti-cancer medication, binds to the minor groove of ctDNA.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET exon 14 mutation
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Tepmetko (tepotinib)
12ms
A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2) (clinicaltrials.gov)
P2, N=120, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Sep 2023 --> May 2024
Trial completion date
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification
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Tagrisso (osimertinib) • Tepmetko (tepotinib)