Non-small Cell Lung Cancer
Conditions
Interventions
investigational material(s)
Generic name etc : Tepotinib and Osimertinib
INN of investigational material : Tepotinib and Osimertinib
Therapeutic category code : 429 Other antitumor agents
Dosage and A
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed by either histology or cytology) with documented activating Epidermal Growth Factor Receptor (EGFR) mutation 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks 3. Acquired resistance on previous first-line osimertinib. Participants must meet both of the following 2 criteria: - Radiological documentation of disease progression on first-line osimertinib - Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last less than 6 months after initiation of osimertinib 4. Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting 5. MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening - Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing - Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment 6. Other protocol defined inclusion criteria could apply
Exclusion criteria
Exclusion criteria: -Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention -Any unresolved toxicity Grade 2 or more according to National cancer institute common terminology criteria for adverse events( NCI-CTCAE) version 5, from previous anticancer therapy with the exception of alopecia -Inadequate hematological, liver and renal function -Impaired cardiac function -History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment -Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 millimeter of mercury (mmHg) -Contraindication to the administration of osimertinib -Other protocol defined exclusion criteria could apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety efficacy 1. Safety run-in: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version (NCI-CTCAE v 5.0) [ Time Frame: Up to Day 21 of Cycle 1 (each Cycle is of 21 days) ] 2. Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as per Independent Review Committee for Combined Therapy in Participants With MET Amplification Determined Centrally by Fluorescence in situ Hybridization(FISH) [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 38 months) ] Participants are identified as having an objective response if they achieve either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progression disease (PD) according to determined according to RECIST 1.1 as adjudicated by the IRC. CR: Complete Response 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 less than (<) 10 mm. Partial response defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as 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. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy 1.To assess the efficacy of tepotinib combined with osimertinib in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification determined centrally by blood-based next generation sequencing.; Objective response (CR or PR) determined according to RECIST Version 1.1 as per IRC. 2.To assess the efficacy of tepotinib monotherapy in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification determined centrally by FISH.; Objective response (CR or PR) determined according to RECIST Version 1.1 as per IRC. 3.To assess tolerability and safety in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification treated with the combination of tepotinib plus osimertinib.: - Occurrence of Adverse Events (AEs) and treatment related AEs. - 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). 4.To assess tolerability and safety in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification treated with tepotinib monotherapy.; - Occurrence of AEs and treatment related AEs. - 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 ECOG performance status. - Occurrence of clinically significantly abnormal ECGs. 5.To further assess efficacy of tepotinib combined with osimertinib in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH.; - Objective response according to RECIST Version 1.1 assessed by Investigator. - Confirmed CR assessed by IRC and by Investigator. - Duration of response assessed from CR or PR | — |
Countries
Asia except Japan, Europe, Japan, North America
Outcome results
None listed