Overview

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

Status:
Completed
Trial end date:
2021-08-12
Target enrollment:
0
Participant gender:
All
Summary
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).
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Merck KGaA
Merck KGaA, Darmstadt, Germany
Treatments:
Carboplatin
Cisplatin
Gefitinib
Pemetrexed
Tepotinib
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.