Locally advanced or Metastatic Non small Cell Lung Cancer (NSCLC)
Conditions
Interventions
investigational material(s)
Generic name etc : Tepotinib
INN of investigational material : Teptinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational
Sponsors
Merck KGaA,(for Japan) Merck Serono Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase Ib Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC), regardless of histology subtype, which failed on gefitinib for reasons other than toxicity or compliance Availability of a fresh or archived pretreatment tumor biopsy (excluding fine needle aspiration and cytology samples). For subjects who have had at least 1 prior anticancer treatment, a biopsy obtained between failure of the most recent anticancer treatment and enrollment is mandatory. Mesenchymal-epithelial transition diagnostic-positive (status) (MET+ status), as determined by the central laboratory. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Other protocol defined inclusion criteria could apply. Phase II Locally advanced or metastatic NSCLC other than predominantly squamous histology (confirmed by either histology or cytology). Activating mutation of the epidermal growth factor (EGFR) receptor (documented, or as determined by the central laboratory). Acquired resistance on first line EGFR-Tyrosine Kinase Inhibitors(TKI)therapy including gefitinib, erlotinib, icotinib, or afatinib. EGFR T790M status after acquired resistance to first line EGFR-TKI therapy including gefitinib, erlotinib, icotinib, or afatinib treatment (as determined by the central laboratory, using a validated PCR test). T790M negative status for the randomized part. T790M positive status for the single-arm cohort (mainland China sites only). Availability of a fresh or archived tumor tissue (excluding fine needle aspiration and cytology samples) obtained between documentation of acquired resistance to gefitinib, erlotinib, icotinib, or afatinib and enrollment is mandatory. MET+ status, as determined by the central laboratory, i.e. c-Met overexpression as determined by IHC (i.e., IHC 2+ or IHC 3+) and/or c-Met amplification and/or increased c-Met gene copy number (GCN), both determined by ISH. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Other protocol defined inclusion criteria could apply
Exclusion criteria
Exclusion criteria: (Phase I and II): Estimated life expectancy less than (<) 3 months. Inadequate bone marrow, liver or renal functions. Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment (Phase 1b only). Prior systemic anticancer treatment with chemotherapy or other agents targeting the EGFR pathway excluding gefitinib, erlotinib, icotinib, and afatinib for advanced NSCLC (one course of chemotherapy regimen for [neo] adjuvant purpose, or one course of chemoradiation for Stage IIIa disease is allowed) (Phase 2 only). Other protocol defined exclusion criteria could apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy exploratory 1. Phase 1b: Number of subjects experiencing at least one dose limiting toxicity (DLT) [ Time Frame: Up to Day 21 of Cycle 1 ] 2. Phase 1b: Percentage of subjects with adverse events (AEs) [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ] 3. Phase 2 (randomized): Progression free survival (PFS) time: Investigator assessments or site radiologist assessment [ Time Frame: Up to 8 months ] PFS (assessed by investigator/site radiologist) time is defined as the time (in months) from randomization to either the first disease progression (PD) per RECIST Version 1.1 or death in T790M negative, MET+ subjects due to any cause within 84 days of either randomization or last tumor assessment. If no progression or death is observed, or if death without previously documented PD is observed after more than 84 days of last tumor assessment without progression, the PFS time will be censored on the date of last tumor assessment/date of randomization, whatever occurs later. | — |
Secondary
| Measure | Time frame |
|---|---|
| safety 1. Phase 2 (randomized): Progression free survival (PFS) time: Independent review assessments [ Time Frame: Time from randomization to the date of death or up to 8 months whichever occur first ] PFS time is defined as the time (in months) from randomization either the first observation of PD (as assessed by the independent review committee) or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. 2. Phase 2 (single arm cohort): Progression free survival (PFS) time: Investigator and Independent review assessment [ Time Frame: Time from first administration of trial treatment to the date of death or up to 8 months whichever occur first ] PFS time is defined as the time (in months) from the first administration of the trial treatment to either the first observation of documented PD per RECIST Version 1.1 or occurrence of death due to any cause within 84 days of either the first administration of the trial treatment or the last tumor assessment. 3. Overall Survival (OS) Time [ Time Frame: Time from randomization to the date of death or up to 10 months whichever occur first ] OS time is defined as the time (in months) from randomization/the first administration of the trial treatment to the date of death in the randomized part of Phase 2/the single-arm cohort of Phase 2 4. Percentage of subjects with objective response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) criteria [ Time Frame: Every 6 weeks until Week 72 and every 12 weeks after Week 72 until radiologically documented progressive disease, death, end of trial, or starting a new treatment, whichever occurs first(assessed up to 3.5 years) ] Objective response is defined as complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the trial treatment to the first observation of PD. 5. Percentage of subject | — |
Countries
Asia except Japan, Japan
Outcome results
None listed