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

NCT03647488 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CINC280D22012018-001420-19
• Study Type: interventional
• Target: 18
• Locations: 6 countries
• Sites: 8

Brief Summary

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-small-cell lung carcinoma; Non-small-cell lung cancer; NSCLC; epidermal growth factor receptor wild type; EGFRwt; Anaplastic lymphoma kinase negative; ALK-; INC280; capmatinib and spartalizumab; combination therapy; docetaxel

Outcome Measures

Primary Outcomes (6)

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

  A DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

  From the day of the first dose of study medication up to 56 days

• Run-in Part: Percentage of Participants With Adverse Events (AEs)

  Percentage of participants with AEs, including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: Death

  From the day of the first dose of study medication to 150 days after the last dose of spartalizumab, or 30 days after the last dose of capmatinib (whichever is later) up to maximum duration of approximately 1.7 years

• Run-in Part: Percentage of Participants With at Least One Dose Reduction.

  Percentage of participants with at least one dose reduction. Dose reductions were only allowed for capmatinib

  From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

• Run-in Part: Percentage of Participants With at Least One Dose Interruption

  Percentage of participants with at least one dose interruption. Dose interruptions were allowed for capmatinib and spartalizumab.

  From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

• Run-in Part: Relative Dose Intensity Received by Participants

  The relative dose intensity of capmatinib and spartalizumab is computed as the ratio of dose intensity and planned dose intensity, multiplied by 100.

  From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

• Randomized Part: Overall Survival (OS)

  OS is defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. Results are not available because randomized part never started.

  From start of treatment to death due to any cause, assessed until the end of the study (up to a planned duration of 18 months)

Secondary Outcomes (15)

• Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment

  From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)

• Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment

  From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)

• Progression Free Survival (PFS)

  From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part)

• Time to Response (TTR) Based on RECIST 1.1 and as Per Investigator Assessment

  From start of treatment to the first documented response of either complete response or partial response, assessed up to 68 weeks (run-in part)

• Duration of Response (DOR) Based on RECIST 1.1 and as Per Investigator Assessment

  From first documented response (CR or PR) to first documented progression or death, whichever came first, assessed up to 68 weeks (run-in part)

Study Arms (3)

Run-in part: capmatinib + spartalizumab

EXPERIMENTAL

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

Drug: Capmatinib; Drug: Spartalizumab

Randomized part: capmatinib+spartalizumab

EXPERIMENTAL

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

Drug: Capmatinib; Drug: Spartalizumab

Randomized part: docetaxel

ACTIVE COMPARATOR

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

Drug: Docetaxel

Interventions

Capmatinib DRUG

Capmatinib 400 mg (tablets) orally taken twice daily

Also known as: INC280

Randomized part: capmatinib+spartalizumab; Run-in part: capmatinib + spartalizumab

Spartalizumab DRUG

Spartalizumab 400 mg via intravenous infusion once every 28 days

Also known as: PDR001

Randomized part: capmatinib+spartalizumab; Run-in part: capmatinib + spartalizumab

Docetaxel DRUG

Docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days

Randomized part: docetaxel

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Grenoble, 38043, France

Location

Novartis Investigative Site

Lille Cédex, 59037, France

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Related Links

• Plain language trial summaries are available on this link

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinib; spartalizumab; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Run-in part was single group. Randomized part (parallel design) was not opened.

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 27, 2018
• Study Start: December 26, 2018
• Primary Completion: September 7, 2020
• Study Completion: September 7, 2020
• Last Updated: January 24, 2022
• Results First Posted: October 25, 2021

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1); BE (1); ES (2); IL (1); DE (1); FR (2)