Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tepotinib · 3 trials · 4 indications
Assessing the antitumour activity of tepotinib in combination with pembrolizumab using the overall response rate as defined by disease response using iRECIST
The area under the plasma concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time profile.
DLT: defined using NCI-CTCAE for AEs Version 4.0, as any of following toxicities: Grade 4 neutropenia for more than 7 days; greater than or equal to (\>=) Grade 3 febrile neutropenia for more than 1 day; Grade 4 or Grade 3 thrombocytopenia with nontraumatic bleeding; \>=Grade 3 uncontrolled nausea/vomiting and/or diarrhoea despite adequate treatment for more than 3 days; \>=Grade 3 any non-hematological AE. (DLT defined specifically for following cases: \>=Grade 3 liver AE requiring recovery period of more than 7 days or to Grade 1 or less or Grade 2 with liver metastases ; \>=Grade 3 lipase and/or amylase elevation with confirmation of pancreatitis. An isolated lipase and/or amylase elevation of \>=Grade 3 without clinical/radiological evidence of pancreatitis was not classified as DLT); and AEs assessed by investigators to be exclusively related to the participant's underlying disease or medical condition/concomitant treatment are not considered as DLTs.
PFS status was evaluated by the number of participants who were progression-free at 12 weeks according to RECIST Version 1.1. Participants were considered to be progression-free if the participant had a tumor assessment of Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeter (mm). Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters, or Stable Disease (SD) defined as any cases that do not qualify for either partial response or progressive disease (an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started)12 weeks after start of treatment or later.
| Arm | Type | Description |
|---|---|---|
| Part A- Escalation | EXPERIMENTAL | The safety run-in part of the study will enrol 6-12 patients. Tepotinib will be given to patients daily for three weeks. After thee weeks, patients will be given pembrolizumab immunotherapy on a 21-day cycle along side tepotinib daily. Dose de-escalation of Tepotinib only will be performed in in Part A.. Should dose level 1 (500mg OD) be deemed non-tolerable by the SRC then a single dose de-escalation to dose level -1 (250mg OD) may be performed. Alternative dosing schedules may be explored. Recruitment into Part A will be staggered such that at least 7 days elapse between treatment of the 1st and 2nd patient of each dose level. In the dose confirmation phase, the study will first evaluate the dose level 1 with 3 patients, expanding to a maximum of 6 evaluable patients. If needed, a maximum of 6 patients will be evaluate in the dose level -1. Recruitment to this arm is closed. |
| Part B- Expansion | EXPERIMENTAL | The expansion part of the study will enrol 13-26 patients with NSCLC and MET exon 14 skipping mutations. The combination of tepotinib and pembrolizumab will be tested throughout this part of the study. The first cycle will test the safety run-in of tepotinib followed by the introduction of combination with pembrolizumab from cycle 2 onwards. Recruitment to this arm is open. |
| Healthy Participants (Control) | EXPERIMENTAL | Participants with normal hepatic function matched to moderate hepatic impairment received single oral dose of 500 milligrams (mg) of tepotinib film-coated tablet on Day 1 after a standard breakfast. |
| Mild Hepatic Impairment (Child-Pugh Class A) | EXPERIMENTAL | Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. |
| Moderate Hepatic Impairment (Child-Pugh Class B) | EXPERIMENTAL | Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. |
| Phase 1b: Tepotinib 300 mg | EXPERIMENTAL | - |
| Phase 1b: Tepotinib 500 mg | EXPERIMENTAL | - |
| Phase 2: Tepotinib 500 mg | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Tepotinib | DRUG | Tepotinib hydrochloride hydrate will be supplied as film coated tablets. The 250 mg oval, white-pink film-coated tablets contain the excipients mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and Opadry II pink. All formulations are intended for oral administration. Refer to pharmacy manual for formulation and strength information. |
| Pembrolizumab | DRUG | Pembrolizumab Solution for Infusion 100 mg/vial is a liquid drug product supplied as a clear to opalescent solution, essentially free of visible particles, in Type I glass vials and manufactured using the fully formulated drug substance with L-histidine as buffering agent, polysorbate 80 as surfactant, and sucrose as stabilizer/tonicity modifier. Pembrolizumab Solution for Infusion can be further diluted with normal saline or 5% dextrose in the concentration range of 1 to 10 mg/mL in IV containers made of polyvinyl chloride (PVC) or non-PVC material. |
Inclusion criteria: 1\. Male or female patients aged 18 or over; 2. Non-small cell lung cancer histologically confirmed; 3. Part A: Either a) Exon 14 MET mutation (on tissue or ctDNA testing); b) Patients have not received prior immunotherapy; c) Patients who have received previous MET inhibitor...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GE Healthcare Technologies Inc. | GEHC | 1 | PHASE1 | GEH200520/ GEH200521- Part A |
| Zimmer Biomet Holdings, Inc. | ZBH | 1 | - | Undisclosed |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | Olverembatinib |
Tepotinib is an investigational small molecule being studied for use in advanced cancer, hepatocellular carcinoma, and non-small cell lung cancer. It is also used in clinical trials involving healthy volunteers to assess drug formulation and interactions. The drug is in Phase 1 clinical development and is not yet approved.
Tepotinib is a kinase inhibitor, as indicated by its '-tinib' suffix, which denotes its target class. It is designed to inhibit specific kinases involved in cancer cell growth and survival. The drug is being evaluated in oncology settings for its potential to treat advanced solid tumors.
Tepotinib is developed by Merck KGaA, a German multinational pharmaceutical company. The company's stock is traded under the ticker MKGAF. Merck KGaA is conducting clinical trials to evaluate the drug's safety and efficacy in various cancer indications.
Tepotinib is currently in Phase 1 clinical development. All completed trials are Phase 1 studies, and there is one active Phase 1 trial ongoing. The drug is investigational and has not received FDA approval for any indication.
Tepotinib has been studied in several Phase 1 trials. Completed trials include NCT03021642, NCT04204902, and NCT05203822, all in healthy volunteers. An active trial, NCT05782361, is studying Tepotinib in combination with pembrolizumab in non-small cell lung cancer.
Tepotinib is the sole name provided for this drug in the available data. No alternative names or aliases have been reported. It is important to refer to the drug by its generic name, Tepotinib, when searching for clinical trial information.