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 1st / 2nd Generation EGFR-TKI or Osimertinib Therapy and Whose Tumors Are T790M Mutation Negative and Harbor MET Amplification (GEOMETRY-E)
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Registration Number
- JPRN-jRCT2041210072
- Lead Sponsor
- Suzuki Kazuyuki
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 245
Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations known to be associated with EGFR TKI sensitivity, T790M negative and MET gene amplification
- Stage IIIB/IIIC NSCLC
- Patients must have failed maximum one prior line of therapy (either to 1st/2nd generation EGFR TKIs or osimertinib) 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
- Prior treatment with any MET inhibitor or HGF-targeting therapy
- Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have 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 has 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Run-in part: Incidence of dose limiting toxicities (DLTs) [ Time Frame: 3 weeks ]<br>Incidence of Dose Limiting Toxicities (DLT) during the first 21 days (3 weeks) of treatment for each dose level associated with administration of capmatinib in combination with osimertinib<br><br>2. Randomized part: Progression free survival (PFS) [ Time Frame: 37 months ]<br>Progression free survival (PFS) per Blinded Independent Review Committee (BIRC) according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1)
- Secondary Outcome Measures
Name Time Method