Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Capmatinib; Osimertinib; Pemetrexed; Cisplatin; Carboplatin
Intervention description: Capmatinib was available as a film-coated tablet for oral use, with a strength of either 150 mg or 200 mg. The initial dose of the combination therapy consisted of capmatinib 400 mg administered orally twice daily (b.i.d).; Osimertinib was available as a tablet for oral use, with a strength of either 80 mg or 40 mg. The initial dose of the combination therapy consisted of osimertinib 80 mg administered orally once per day (q.d); Pemetrexed concentrate for solution for intravenous use was to be administered intravenously. The procurement of pemetrexed was to be done locally, following local practices and regulations.; Cisplatin concentrate for solution for intravenous use was to beadministered intravenously during the study. The procurement of cisplatin was to be done locally, following local practices and regulations.; Carboplatin concentrate for solution for intravenous use was to be administered intravenously during the study. The procurement of carboplatin was to be done locally, following local practices and regulations.
Intervention MeSH terms: Carboplatin; Pemetrexed; Osimertinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: INC280; capmatinib; osimertinib; pemetrexed; platinum-based chemotherapy; NSCLC; Non-Small Cell Lung Cancer; Carcinoma; EGFR Mutation; T790M negative; MET amplification; second line therapy; GEOMETRY; GEOMETRY-E

Summary:

      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).
    

Eligibility criteria:

        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