A Phase III Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib in Combination With Osimertinib Versus Platinum - Pemetrexed Based Doublet Chemotherapy in Patients With Locally Advanced or Metastatic NSCLC Harboring EGFR Activating Mutations Who Have Progressed on Prior Generation EGFR-TKI Therapy and Whose Tumors Are T790M Mutation Negative and Harbor MET Amplification (GEOMETRY-E)

CINC280L12301

This study aimed to evaluate the anticancer activity of capmatinib in combination with osimertinib compared to platinum-pemetrexed based doublet chemotherapy as second line treatment in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who progressed following EGFR tyrosine kinase inhibitors (TKIs).

2021-09-22

2022-12-27

2022-12-27

Terminated

Early phase I

6

Key Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations known to be associated with EGFR TKI sensitivity, EGFR T790M negative and MET gene amplification * Stage IIIB/IIIC or IV NSCLC * Participants must have progressed on one prior line of therapy (1st/2nd generation EGFR TKIs, osimertinib or other third generation EGFR TKIs) for advanced/metastatic disease (stage IIIB/IIIC and must be candidates for platinum (cisplatin or carboplatin) - pemetrexed doublet based chemotherapy * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Participants must have recovered from all toxicities related to prior systemic therapy to grade ≤ 1 Common Terminology Criteria Adverse Event 5.0 (CTCAE v 5.0) * At least one measurable lesion as defined by RECIST 1.1 * Participants must have adequate organ function Key Exclusion Criteria: * Prior treatment with any MET inhibitor or HGF-targeting therapy * Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms * Carcinomatous meningitis * Presence or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years * Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis * Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome * Clinically significant, uncontrolled heart diseases * known druggable molecular alterations that may render participants eligible for alternative targeted therapies

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "The study was terminated early based on Sponsor's decision unrelated to any safety concerns and the randomized part of the study was not initiated", 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 6, 'type': 'ACTUAL'}}

2024-03-05