Locally advanced or metastatic NSCLC histology (confirmed by either histology or cytology) with documented activating mutation of the EGFR receptor including T790M status Resistance on previous EGFR-TKI therapy
Conditions
Interventions
Product Name: tepotinib
Product Code: MSC2156119J
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tepotinib
CAS Number: 1100598-30-8
Current Sponsor code: MSC2156119J
Other descriptive n
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are = 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age [ie, = 20 years of age in Japan]), at the time of signing the informed consent. 2. Are participants with the following: a) Locally advanced or metastatic NSCLC histology (confirmed by either histology or cytology) with documented activating mutation of the EGFR receptor including T790M status b) Presence of at least 1 independently verified measurable lesion in accordance with RECIST 1.1, that can be accurately assessed at baseline with = 10 mm in the longest diameter (except lymph nodes which must Have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements and that preferably was not previously irradiated or biopsied c) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks d) Acquired resistance on previous EGFR-TKI therapy. Participants must meet both of the following 2 criteria: -Radiological documentation of disease progression to previous EGFR-TKI therapy. Participants having received 2 or more previous EGFR-TKI containing therapies with/without vascular endothelial growth factor inhibitors need to show disease progression against 3rd generation EGFR-TKI, eg, osimertinib treatment -At least 1 prior objective clinical benefit documented, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last > 6 months) after initiation of previous EGFR-TKI treatment(s) e) Received at least 1 but no more than 4 prior lines of prior therapy in the noncurative advanced or metastatic NSCLC setting f) MET amplification in plasma defined by a positive LBx test, using validated assays with an adequate regulatory status as determined by the Sponsor 3.Woman no WOBCP, or, use a highly effective contraception. Man: Contraception or no intercourse with a WOBCP1. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention. Prior radiotherapy or surgery for brain metastases such as stereotactic radiosurgery/gammaknife must have been completed = 2 weeks, all others = 4 weeks prior to start of therapy. 2. Any unresolved toxicity Grade 2 or more according to NCI-CTCAE version 5, from previous anticancer therapy with the exception of alopecia. 3. Need for transfusion within 14 days prior to the first dose of study intervention. 4. Participants who have brain metastasis as the only measurable lesion 5. Inadequate hematological function: ? Hemoglobin 1.5 × ULN ? AST/ALT/ALP > 3 × ULN ? For participants with liver metastases: i. Total bilirubin > 1.5 × ULN ii. AST/ALT/ALP > 5 × ULN iii. For participants with bone metastases: ALP > 5 × ULN. 7. Inadequate renal function: ? Renal impairment as evidenced by serum creatinine ? 1.5 × ULN, or creatinine clearance (CrCl) 470 ms for women and > 450 ms for men at screening. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes. 11. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg). 12. Contraindication to the administration of osimertinib. 13. Medical history of liver fibrosis/cirrhosis. 14. Past or current history of neoplasm other than NSCLC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years. 15. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product. 16. Major surgery within 28 days prior to Day 1 of study intervention. 17. Known human immunodeficiency virus positivity. 18. Known hypersensitivity to any of the study intervention ingredients. 19. Has not received an EGFR-TKI containing treatment directly prior to enrollment into the study, ie, chemotherapy or checkpoint inhibitor treatment with/without vascular endothelial growth factor inhibitors either in monotherapy or in combination are allowed, if these treatments do not represent the most recent treatment lin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of tepotinib combined with osimertinib in participants with advanced or metastatic NSCLC. Objective response (confirmed complete response [CR] or partial response [PR]) determined according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as per Independent Review Committee (IRC).;Secondary Objective: To assess tolerability and safety. To further assess efficacy. To assess health related quality of life. Pharmacokinetics: Single- and multiple-dose PK profile of osimertinib, tepotinib, and their metabolites including To assess resistance marker related to EGFR and other molecular pathways in circulating tumor deoxyribonucleic acid (ctDNA) at baseline and progression.;Primary end point(s): Objective response (confirmed complete response [CR] or partial response [PR]) determined according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as per Independent Review Committee (IRC).;Timepoint(s) of evaluation of this end point: Cycles of 21 days until disease progression (according to RECIST Version 1.1), death, adverse event leading to discontinuation, study withdrawal or consent withdrawal. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Occurrence of TEAEs and treatment-related AEs according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and deaths. Occurrence of abnormalities (Grade = 3) in laboratory test values (hematology and coagulation, biochemistry) and urinalysis. Occurrence of markedly abnormal vital sign measurements, change in body weight, and Eastern Cooperative Oncology Group (ECOG) performance status. Occurrence of clinically significantly abnormal electrocardiograms (ECGs). Objective response according to RECIST 1.1 assessed by Investigator. Confirmed CR assessed by IRC and by Investigator. Duration of response assessed from CR or PR until PD, death, or last tumor assessment assessed by IRC and by Investigator. Disease control (confirmed CR + PR or stable disease [SD] lasting at least 12 weeks) as assessed by IRC and by Investigator. Progression free survival time according to RECIST 1.1 by IRC and by Investigator. Overall survival. Patient-reported outcomes/health-related quality of life as reported using the following: ? EuroQol Five Dimension Five Level Scale ? European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 Non–small Cell Lung Cancer Symptom Assessment Questionnaire. Single- and multiple-dose PK profile of osimertinib, tepotinib, and their metabolites including but not limited to AUC0-t, Cmax, and tmax after first dose (Day 1) and after multiple study intervention dose administrations (Day 15) (safety run-in). Population PK profile of osimertinib, tepotinib, and their metabolites, including, but not limited to, CL/f and VZ/f based on sparse PK sampling on Day 1, Cycle 1 and 2. Mutation status in EGFR and other pathways;Timepoint(s) of evaluation of this end point: continuous | — |
Countries
Belgium, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Philippines, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, United States, Vietnam
Contacts
Public ContactCommunication Center
Merck KGaA
Outcome results
None listed