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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Gefitinib; Drug: Carboplatin; Drug: Pemetrexed; Drug: Cisplatin; Drug: Tepotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01982955

2016-001604-28 (EudraCT Number)

EMR 200095-006

Details and patient eligibility

About

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).

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Phase Ib

Inclusion Criteria:

• 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 pre treatment tumor biopsy (excluding fine needle aspiration and cytology samples). For participants who have had at least 1 prior anticancer treatment, a biopsy obtained between failure of the most recent anticancer treatment and enrolment 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

Inclusion criteria:

• 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 (EGFR-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 (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 study 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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88 participants in 5 patient groups

Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg

Experimental group

Description:

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.

Treatment:

Drug: Tepotinib

Drug: Gefitinib

Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg

Experimental group

Description:

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.

Treatment:

Drug: Tepotinib

Drug: Gefitinib

Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 negative)

Experimental group

Description:

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.

Treatment:

Drug: Tepotinib

Drug: Gefitinib

Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 negative)

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Drug: Cisplatin

Phase 2: Single-arm Cohort (MET+ T790M positive)

Experimental group

Description:

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.

Treatment:

Drug: Tepotinib

Drug: Gefitinib