Tepotinib With Gefitinib in Participants With Locally Advanced or Metastatic NSCLC (INSIGHT)

Sponsor
Merck KGaA, Darmstadt, Germany
Study ID
NCT01982955
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tepotinib — DRUG
    Tepotinib was administered at a dose range of 300 or 500 milligram (mg) (Phase 1b) and the recommended phase II dose (RP2D) determined in the Phase 1b in Phase II orally once daily over a 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment. RP2D was determined as per safety monitoring committee (SMC) discretion.
  • Gefitinib — DRUG
    Gefitinib was administered at a dose of 250 mg orally as once daily over a 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment.
  • Pemetrexed — DRUG
    Pemetrexed was administered at a dose of 500 milligram per square meter (mg/m\^2) as intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment or up to 6 cycles if pemetrexed maintenance is not considered.
  • Cisplatin — DRUG
    Cisplatin was administered at a dose of 75 mg/m\^2 as intravenous infusion over 2 hours on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment or up to 6 cycles if pemetrexed maintenance is not considered.
  • Carboplatin — DRUG
    Carboplatin was administered intravenously on Day 1 of each 21-day cycle at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator until progressive disease, intolerable toxicity, participants withdrawal from treatment or up to 6 cycles if pemetrexed maintenance is not considered.

Study Details

This is a multi-center, open-label, randomized, Phase 1b/2 study to determine the recommended phase 2 dose (RP2D) and to evaluate the efficacy in terms of progression free survival (PFS) of Tepotinib when used in combination with gefitinib in partcipants with T790M negative, MET positive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation and having acquired resistance to Prior EGFR-Tyrosine Kinase Inhibitor (EGFR-TKI) Therapy. This study has 2:1 randomization (Tepotinib/Gefitinib arm versus Chemotherapy arm).

Key Dates

Start date
Dec 23, 2013
Status verified
Oct 2022
Primary completion
Dec 12, 2017
Completion
Oct 14, 2021

Study Design

Enrollment
88 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg
    Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
  • Experimental: Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
    Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
  • Experimental: Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 negative)
    Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
  • Experimental: Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 negative)
    Participants randomized to receive 500 milligram per square meter (mg/m\^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
  • Experimental: Phase 2: Single-arm Cohort (MET+ T790M positive)
    Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.

Primary Outcome Measure

Phase 1b: Number of Participants Experiencing at Least One Dose Limiting Toxicity (DLT) [ Time Frame: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days) ]

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