Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Non-small Cell Lung Cancer

Novartis

Status and phase: Completed; Phase 2

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Docetaxel; Drug: Spartalizumab; Drug: Capmatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03647488

CINC280D2201

2018-001420-19 (EudraCT Number)

Details and patient eligibility

About

The purpose of this trial was to evaluate the safety and efficacy of capmatinib in combination with spartalizumab in adult participants with epidermal growth factor receptor (EGFR) wild type (for exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative in locally advanced (stage IIIB, not eligible for definitive chemo-radiation) or metastatic (stage IV) Non-small cell lung cancer (NSCLC) after failure of platinum doublet and checkpoint inhibitor treatment.

Full description

This was a two-part prospectively designed, multicenter, open-label, randomized phase II study.

Part 1: Run-in. Prior to the randomized part of the study, a run-in to assess the safety and tolerability as well as preliminary efficacy of the capmatinib and spartalizumab combination was conducted. Participants were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days. A review was planned to take place after all participants had at least 24 weeks of follow-up. The decision to expand the study to the randomized part was to be based on the safety, tolerability, and preliminary efficacy of the capmatinib and spartalizumab combination.

Part 2: Randomized. Subjects were planned to be randomized to one of the following arms in a 2:1 ratio: 1) combination of capmatinib 400 mg BID and spartalizumab 400 mg i.v. once every 28 days; 2) docetaxel 75 mg/m2 i.v. following local guidelines as per standard of care and product labels. Based on the results obtained in the run-in part of the study, the randomized part was not opened.

For the run-in part of the study, the treatment period began on Cycle 1 Day 1 and continued in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of informed consent, pregnancy, lost to follow-up, or death irrespective of start of new anti-neoplastic therapy. After treatment discontinuation, all subjects were followed for safety evaluations during the safety follow-up period, and the subject's status was collected every 8 weeks as part of the survival follow-up

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed locally advanced/metastatic (stage IIIB/IV), EGFR wild-type, ALK rearrangement negative, non-small cell lung cancer
• Subject had demonstrated progression following one prior platinum doublet and one prior PD-(L)1 checkpoint inhibitor (either alone or in combination, the most recent treatment regimen must have contained a PD-(L)1 checkpoint inhibitor)
• Subjects must be candidates for single agent docetaxel
• Subjects must have at least one lesion evaluable by RECIST 1.1

Exclusion criteria

• Prior treatment with a MET inhibitor or HGF (Hepatocyte growth factor) targeting therapy
• Any untreated central nervous system (CNS) lesion
• Use of any live vaccines against infectious diseases within 12 weeks of initiation of study treatment.

Other protocol-defined inclusion/exclusion criteria might apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Run-in part: capmatinib + spartalizumab

Experimental group

Description:

Participants (enrolled in the run-in part) were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days

Treatment:

Drug: Capmatinib

Drug: Spartalizumab

Randomized part: capmatinib+spartalizumab

Experimental group

Description:

Participants (enrolled in the randomized part) treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days

Treatment:

Drug: Capmatinib

Drug: Spartalizumab

Randomized part: docetaxel

Active Comparator group

Description:

Participants (enrolled in the randomized part) treated with docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days

Treatment:

Drug: Docetaxel