Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy

NCT04816214 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CINC280L123012020-003677-21
• Study Type: interventional
• Target: 6
• Locations: 3 countries
• Sites: 4

Brief 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).

Conditions

Carcinoma, Non-Small-Cell Lung

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

Outcome Measures

Primary Outcomes (2)

• Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)

  A DLT was defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, progressive disease, inter-current illness, or concomitant medications, that despite optimal therapeutic intervention that occurred within the first 21 days of treatment with capmatinib in combination with osimertinib.

  Up to 21 Days

• Randomized Part: Progression Free Survival (PFS) Based on BIRC Assessment

  PFS was defined as time from date of randomization to the date of first documented disease progression (PD) based on Blinded Independent Review Committee (BIRC) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurred first. Progression was defined as a ≥20% increase in sum of longest diameters (SLD) compared to smallest SLD in the study, or progression of non-target lesions or new lesions.

  From randomization to first documented progression or deaths, planned to be assessed up to 37 months

Secondary Outcomes (33)

• Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug

  From the first dose until last dose of study treatment, assessed up to 39 weeks

• Run-in Part: Dose Intensity of Each Study Drug

  From the first dose until last dose of study treatment, assessed up to 39 weeks

• Run-in Part: Median Duration of Exposure to Each Study Drug

  From the first dose until last dose of study treatment, assessed up to 39 weeks

• Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib

  Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

• Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

  Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Study Arms (3)

Run-in part: Capmatinib + Osimertinib

EXPERIMENTAL

In the run-in part, up to two dose levels of capmatinib in combination with osimertinib were planned to be investigated. The initial dose level for the combination therapy was capmatinib 400 mg orally twice daily (b.i.d) and osimertinib 80 mg orally once per day (q.d). If a dose de-escalation was necessary, a lower dose level was defined as capmatinib 400 mg orally b.i.d and osimertinib 40 mg orally q.d.

Drug: Capmatinib; Drug: Osimertinib

Randomized part: Capmatinib + Osimertinib

EXPERIMENTAL

In the randomized part, capmatinib in combination with osimertinib was to be administered at the recommended Phase III regimen (defined in the safety run-in part). The study was terminated early based on Sponsor's decision unrelated to safety concerns and the randomized part of the study was not initiated.

Drug: Capmatinib; Drug: Osimertinib

Randomized Part: Platinum + Pemetrexed Based Doublet Chemotherapy

ACTIVE COMPARATOR

In the randomized part, platinum-pemetrexed based doublet chemotherapy was to follow local guidelines as per standard of care and products labels. Participants randomized to platinum-pemetrexed based doublet chemotherapy arm were to be allowed to crossover to receive capmatinib in combination with osimertinib. The study was terminated early based on Sponsor's decision unrelated to safety concerns and the randomized part of the study was not initiated.

Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Interventions

Capmatinib DRUG

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).

Also known as: INC280

Randomized part: Capmatinib + Osimertinib; Run-in part: Capmatinib + Osimertinib

Osimertinib DRUG

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)

Randomized part: Capmatinib + Osimertinib; Run-in part: Capmatinib + Osimertinib

Pemetrexed DRUG

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.

Randomized Part: Platinum + Pemetrexed Based Doublet Chemotherapy

Cisplatin DRUG

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.

Randomized Part: Platinum + Pemetrexed Based Doublet Chemotherapy

Carboplatin DRUG

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.

Randomized Part: Platinum + Pemetrexed Based Doublet Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Sunto Gun, Shizuoka, 411 8777, Japan

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Related Links

• Plain Language Trial Summary

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma

Interventions

capmatinib; osimertinib; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 25, 2021
• Study Start: September 22, 2021
• Primary Completion: December 27, 2022
• Study Completion: December 27, 2022
• Last Updated: March 5, 2024
• Results First Posted: October 30, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (2); KR (1); SG (1)