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

NCT ID: NCT04816214

Last Updated: 2024-03-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-22
• Study Completion Date: 2022-12-27

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).

Detailed Description

This was a multicenter, open-label, randomized, active-controlled, global phase III study that enrolled adult participants with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) activating mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who had progressed following EGFR tyrosine kinase inhibitors (TKIs).

The study was conducted in two parts. The initial part was a safety run-in part, which aimed at assessing the safety and tolerability of capmatinib in combination with osimertinib and at determining the recommended dosage for the subsequent randomized part. The randomized part compared the efficacy and safety of capmatinib in combination with osimertinib to a platinum-based doublet chemotherapy regimen using either cisplatin or carboplatin, combined with pemetrexed, as second-line treatment.The randomized part was not initiated.

In the randomized part (if initiated), participants were to receive their assigned treatment (either capmatinib in combination with osimertinib or platinum-pemetrexed based doublet chemotherapy) until they experienced any of the following: documented disease progression according to the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) as assessed by the investigator during the run-in part and confirmed by a blinded independent review committee (BIRC) during the randomized part, withdrawal of consent, pregnancy, lost to follow-up, or death. Participants who progressed in the platinum-pemetrexed arm were to be permitted to switch to capmatinib in combination with osimertinib therapy after BIRC-confirmed, RECIST 1.1-defined progressive disease. If, in the judgment of the investigator, there was evidence of clinical benefit and the participant wished to continue, study treatment could be continued beyond the initial disease progression according to RECIST 1.1 criteria. After treatment discontinuation, all participants were to be followed for safety evaluations during the safety follow-up period.

On 11-May-2022, Novartis decided to halt enrollment for this study due to a business consideration unrelated to any safety concerns. Ongoing patients in the run-in part were allowed to continue treatment through other post-trial drug supply options, as applicable. On 27-Dec-2022 the last patient was transitioned off the study, and following the study protocol this date was declared the Global end of trial date. Randomized part was not initiated.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Run-in part: Capmatinib + Osimertinib

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.

Group Type: EXPERIMENTAL

Capmatinib

Intervention Type: 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).

Osimertinib

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

Capmatinib

Intervention Type: 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).

Osimertinib

Intervention Type: 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: Platinum + Pemetrexed Based Doublet Chemotherapy

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.

Group Type: ACTIVE_COMPARATOR

Pemetrexed

Intervention Type: 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.

Cisplatin

Intervention Type: 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.

Carboplatin

Intervention Type: 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.

Interventions

Capmatinib

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).

Intervention Type: DRUG

Osimertinib

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)

Intervention Type: DRUG

Pemetrexed

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.

Intervention Type: DRUG

Cisplatin

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.

Intervention Type: DRUG

Carboplatin

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 Type: DRUG

Other Intervention Names

INC280

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Kashiwa, Chiba, Japan

Novartis Investigative Site

Sunto Gun, Shizuoka, Japan

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, , South Korea

Countries

Japan; Singapore; South Korea

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1727

Plain Language Trial Summary

Other Identifiers

2020-003677-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CINC280L12301

Identifier Type: -

Identifier Source: org_study_id