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)

JRCT ID: jRCT2041210072

Registered date:16/09/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Carcinoma, Non-Small-Cell Lung
• Date of first enrollment: 02/12/2021
• Target sample size: 245
• Countries of recruitment: Hong Kong,Japan,Republic of India,Japan,Republic of Korea,Japan,Malaysia,Japan,Republic of Singapore,Japan,Taiwan,Japan,Kingdom of Thailand,Japan,Socialist Republic of Viet Nam,Japan,People's Republic of China,Japan,Republic of Austria,Japan,Republic of Bulgaria,Japan,Republic of Croatia,Japan,French Republic,Japan,Federal Republic of Germany,Japan,Republic of Hungary,Japan,State of Israel,Japan,Republic of Italy,Japan,Republic of Lithuania,Japan,Kingdom of the Netherlands,Japan,Republic of Poland,Japan,Portuguese Republic,Japan,Romania,Japan,Russian Federation,Japan,United States of America,Japan,Republic of Slovenia,Japan,Kingdom of Spain,Japan,United Kingdom of Great Britain and Northern Irela,Japan,Argentine Republic,Japan,Republic of Chile,Japan,Republic of Colombia,Japan
• Study type: Interventional

Intervention(s)

- Drug: capmatinib
film-coated tablet for oral use
Other Name: INC280
- Drug: osimertinib
tablet for oral use
Other Names:Tagrisso, Tagrix
- Drug: pemetrexed
concentrate for solution for intravenous use
Other Names:Alimta, Pleumet, Pemecad, Pemfexy
- Drug: cisplatin
concentrate for solution for intravenous use
- Drug: carboplatin
concentrate for solution for intraven

Outcome(s)

Primary Outcome

1. Run-in part: Incidence of dose limiting toxicities (DLTs) [ Time Frame: 3 weeks ]
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

2. Randomized part: Progression free survival (PFS) [ Time Frame: 37 months ]
Progression free survival (PFS) per Blinded Independent Review Committee (BIRC) according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- 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

Exclude criteria

- 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

Related Information

• Primary Sponsor: Suzuki Kazuyuki
• Secondary ID(s): NCT04816214