systemic clearance of tepotinib  (Merck KGaA)

Journal: Clinical and Translational Science

Article Title: Sensitivity of Tepotinib to Inhibitors or Inducers of CYP3A4 and P‐Gp: Drug Interaction Studies and Physiologically‐Based Pharmacokinetic Analysis

doi: 10.1111/cts.70273

Figure Lengend Snippet: Arithmetic mean (± standard deviation for linear plot) tepotinib plasma concentration‐time profiles for tepotinib administered alone and in the presence of itraconazole. The horizontal line indicates the lower limit of quantification.

Article Snippet: The systemic clearance of tepotinib (as assessed following IV administration) is 12.8 L/h (~3 mL/min/kg), translating to a blood clearance of approximately 3–5 mL/min/kg, based on a blood: plasma ratio of 0.6–1.0 (the healthcare business of Merck KGaA, Darmstadt, Germany; data on file), indicating a hepatic extraction ratio of approximately 0.15–0.25.

Techniques: Standard Deviation, Clinical Proteomics, Concentration Assay

Journal: Clinical and Translational Science

Article Title: Sensitivity of Tepotinib to Inhibitors or Inducers of CYP3A4 and P‐Gp: Drug Interaction Studies and Physiologically‐Based Pharmacokinetic Analysis

doi: 10.1111/cts.70273

Figure Lengend Snippet: Arithmetic mean (± standard deviation for linear plot) tepotinib plasma concentration‐time profiles for tepotinib administered alone and in the presence of carbamazepine. The horizontal line indicates the lower limit of quantification.

Article Snippet: The systemic clearance of tepotinib (as assessed following IV administration) is 12.8 L/h (~3 mL/min/kg), translating to a blood clearance of approximately 3–5 mL/min/kg, based on a blood: plasma ratio of 0.6–1.0 (the healthcare business of Merck KGaA, Darmstadt, Germany; data on file), indicating a hepatic extraction ratio of approximately 0.15–0.25.

Techniques: Standard Deviation, Clinical Proteomics, Concentration Assay

Journal: Clinical and Translational Science

Article Title: Sensitivity of Tepotinib to Inhibitors or Inducers of CYP3A4 and P‐Gp: Drug Interaction Studies and Physiologically‐Based Pharmacokinetic Analysis

doi: 10.1111/cts.70273

Figure Lengend Snippet: Tepotinib PBPK modeling. Panels A and B present simulated mean plasma concentration profiles and 90% prediction intervals (solid lines and shading) and mean observed plasma concentrations (dots) from Study 1 (A, N = 17) and Study 2 (B, N = 18), respectively. (Panel C) presents simulated geometric mean ratios (GMR) with 90% CI ( N = 400) for AUC 0‐∞ and C max (itraconazole coadministration) for different f mCYP3A4 , and with and without contribution of hepatic P‐gp to elimination and observed GMR with 90% CI from Study 1 ( N = 17). AUC, area under the curve; CI, confidence interval; C max , maximal plasma concentration; f mCYP3A4 , fraction metabolized by CYP3A4; GMR, geometric mean ratio; PBPK, physiologically‐based pharmacokinetic.

Article Snippet: The systemic clearance of tepotinib (as assessed following IV administration) is 12.8 L/h (~3 mL/min/kg), translating to a blood clearance of approximately 3–5 mL/min/kg, based on a blood: plasma ratio of 0.6–1.0 (the healthcare business of Merck KGaA, Darmstadt, Germany; data on file), indicating a hepatic extraction ratio of approximately 0.15–0.25.

Techniques: Clinical Proteomics, Concentration Assay

Journal: JRSM Open

Article Title: The UK's Early Access to Medicines Scheme 10 years on: an evaluation using publicly available data

doi: 10.1177/20542704251317916

Figure Lengend Snippet: Drugs submitted to EAMS.

Article Snippet: 13 , Tepotinib , Tepmetko , Advanced non-small cell lung cancer , Merck Serono.

Techniques: Infection, Mutagenesis, Translocation Assay

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Advances in clinical research of MET exon 14 skipping mutations in non-small cell lung cancer

doi: 10.1007/s00432-025-06115-y

Figure Lengend Snippet: Past or ongoing clinical studies of NSCLC with METΔ14ex

Article Snippet: Tepotinib (Ib) , VISION (Globenewswire ) , NCT02864992 , II , 99 , ORR: 46% mPFS: 8.5 , Peripheral edema nausea.

Techniques:

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Advances in clinical research of MET exon 14 skipping mutations in non-small cell lung cancer

doi: 10.1007/s00432-025-06115-y

Figure Lengend Snippet: When and by country the medicines are available

Article Snippet: Tepotinib (Ib) , VISION (Globenewswire ) , NCT02864992 , II , 99 , ORR: 46% mPFS: 8.5 , Peripheral edema nausea.

Techniques:

Journal: Lung cancer (Amsterdam, Netherlands)

Article Title: Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines.

doi: 10.1016/j.lungcan.2025.108415

Figure Lengend Snippet: Fig. 3. Efficacy of tepotinib in ALK-rearranged NSCLC cell lines. (A) Immunoblot analysis of the indicated proteins in H3122, ABC-19, and ABC-11 cells treated with DMSO, tepotinib, alectinib, or their combination for 24 h. B, MTT assay results for H3122, ABC-19, and ABC-11 cells treated with DMSO, tepotinib, alectinib, or their combination for 72 h. Statistical significance is indicated as follows: ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05 from cell and DMSO controls. (C) Crystal violet staining of cancer cells after six days of treatment with 1 μmol/L alectinib combined with 2 μmol/L tepotinib. Alec, alectinib; Tep, tepotinib. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Alectinib [33], erlotinib [34], and tepotinib [35] were purchased from Selleck Chemicals (Houston, TX, USA) and dissolved in dimethyl sulfoxide for in-vitro studies.

Techniques: Western Blot, MTT Assay, Staining

Journal: Lung cancer (Amsterdam, Netherlands)

Article Title: Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines.

doi: 10.1016/j.lungcan.2025.108415

Figure Lengend Snippet: Fig. 4. Effects of PBMC co-culture and Fc receptor inhibition on tumor cell response to drug treatments. (A) Crystal violet staining of tumor cells treated for seven days with PBMCs and drugs. Tumor cells were co-cultured with PBMCs at 5 × 106 cells per well and treated with 1 μmol/L alectinib, 2 μmol/L erlotinib, 2 μmol/L tepotinib, or 1000 μg/mL amivantamab. Alec, alectinib; Erl, erlotinib; Tep, tepotinib; Ami, amivantamab. (B) Crystal violet staining to assess the effect of Fc receptor inhibition on amivantamab in the presence of alectinib and PBMCs. Tumor cells were co-cultured for seven days with 5 × 106 PBMCs per well, treated or untreated with an Fc receptor-binding inhibitor polyclonal antibody, 1 μmol/L alectinib, and 1000 μg/mL amivantamab and then stained with crystal violet. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Alectinib [33], erlotinib [34], and tepotinib [35] were purchased from Selleck Chemicals (Houston, TX, USA) and dissolved in dimethyl sulfoxide for in-vitro studies.

Techniques: Co-Culture Assay, Inhibition, Staining, Cell Culture, Binding Assay