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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03647488
Recruitment Status : Completed
First Posted : August 27, 2018
Results First Posted : October 25, 2021
Last Update Posted : January 24, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Capmatinib Drug: Spartalizumab Drug: Docetaxel Phase 2

Detailed 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Run-in part was single group. Randomized part (parallel design) was not opened.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Multicenter Randomized Two-arm Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Pretreated Adult Patients With EGFR Wild-type ALK Rearrangement Negative Advanced/Metastatic Non-small Cell Lung Cancer
Actual Study Start Date : December 26, 2018
Actual Primary Completion Date : September 7, 2020
Actual Study Completion Date : September 7, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Run-in part: capmatinib + spartalizumab
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
Capmatinib 400 mg (tablets) orally taken twice daily
Other Name: INC280

Drug: Spartalizumab
Spartalizumab 400 mg via intravenous infusion once every 28 days
Other Name: PDR001

Experimental: Randomized part: capmatinib+spartalizumab
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
Capmatinib 400 mg (tablets) orally taken twice daily
Other Name: INC280

Drug: Spartalizumab
Spartalizumab 400 mg via intravenous infusion once every 28 days
Other Name: PDR001

Active Comparator: Randomized part: docetaxel
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
Docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days




Primary Outcome Measures :
  1. Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: From the day of the first dose of study medication up to 56 days ]
    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.

  2. Run-in Part: Percentage of Participants With Adverse Events (AEs) [ Time Frame: 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 ]

    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


  3. Run-in Part: Percentage of Participants With at Least One Dose Reduction. [ Time Frame: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks ]
    Percentage of participants with at least one dose reduction. Dose reductions were only allowed for capmatinib

  4. Run-in Part: Percentage of Participants With at Least One Dose Interruption [ Time Frame: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks ]
    Percentage of participants with at least one dose interruption. Dose interruptions were allowed for capmatinib and spartalizumab.

  5. Run-in Part: Relative Dose Intensity Received by Participants [ Time Frame: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks ]
    The relative dose intensity of capmatinib and spartalizumab is computed as the ratio of dose intensity and planned dose intensity, multiplied by 100.

  6. Randomized Part: Overall Survival (OS) [ Time Frame: 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) ]

    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.



Secondary Outcome Measures :
  1. Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment [ Time Frame: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part) ]

    ORR is defined as the percentage of subjects with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as per investigator assessment.

    CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

    PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    ORR results for randomized part are not available because randomized part never started.


  2. Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment [ Time Frame: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part) ]

    DCR is defined as the percentage of subjects with best overall response of CR or PR or stable disease based on RECIST 1.1 and as per investigator assessment.

    CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

    PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Stable disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

    DCR results for randomized part are not available because randomized part never started.


  3. Progression Free Survival (PFS) [ Time Frame: From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part) ]

    PFS is defined as the time from the date of start of treatment to the date of the first documented radiological progression or death due to any cause. For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.

    Progression is defined using RECIST 1.1 and as per investigator assessment as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    PFS results for randomized part are not available because randomized part never started.


  4. Time to Response (TTR) Based on RECIST 1.1 and as Per Investigator Assessment [ Time Frame: From start of treatment to the first documented response of either complete response or partial response, assessed up to 68 weeks (run-in part) ]

    TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed. TTR was evaluated according to RECIST 1.1 and as per investigator assessment.

    CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

    PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    For run-in part, TTR results are not available because there were no participants achieving response (CR or PR) For randomized part , TTR results are not available because randomized part never started.


  5. Duration of Response (DOR) Based on RECIST 1.1 and as Per Investigator Assessment [ Time Frame: From first documented response (CR or PR) to first documented progression or death, whichever came first, assessed up to 68 weeks (run-in part) ]
    DOR is the time between the date of first documented response(CR or PR) and the date of first documented progression or death due to underlying cancer based on RECIST1.1 and as per investigator assessment. If progression or death has not occurred, the subject is censored at the date of last adequate tumor assessment. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progression: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. The sum must also demonstrate an absolute increase of at least 5 mm. Results are not available because there were no participants achieving response in the run-in part and randomized part never started

  6. AUClast of Capmatinib [ Time Frame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days ]
    AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated using non-compartmental methods.

  7. AUCtau of Capmatinib [ Time Frame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days ]
    AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval Tau. AUCtau was calculated using non-compartmental methods.

  8. Maximum Plasma Concentration (Cmax) of Capmatinib [ Time Frame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days ]
    The maximum (peak) observed plasma concentration after single dose administration. Cmax was calculated using non-compartmental methods.

  9. Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib [ Time Frame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days ]
    Tmax is the time to reach maximum (peak) plasma concentration of capmatinib after single dose administration (time). Tmax was calculated using non-compartmental methods.

  10. AUClast of Spartlizumab [ Time Frame: CCycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days ]
    AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated using non-compartmental methods.

  11. AUCtau of Spartlizumab [ Time Frame: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days ]
    AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval Tau. AUCtau was calculated using non-compartmental methods.

  12. Maximum Plasma Concentration (Cmax) of Spartlizumab [ Time Frame: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days ]
    The maximum (peak) observed plasma concentration after single dose administration. Cmax was calculated using non-compartmental methods.

  13. Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab [ Time Frame: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days ]
    Tmax is the time to reach maximum (peak) plasma concentration of spartlizumab after single dose administration (time). Tmax was calculated using non-compartmental methods.

  14. Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline [ Time Frame: Cycle 1 Day 1 at predose. Each Cycle is 28 days ]
    ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline

  15. Spartalizumab ADA Incidence On-treatment [ Time Frame: Predose at Cycle (C)1 Day (D)1, C2D1, C3D1, C4D1, C6D1, C8D1, C10D1, C12D1, thereafter every 6 cycles until discontinuation, and end of treatment (EOT), 30-day and 150-day after EOT ]
    ADA incidence on treatment was calculated as the proportion of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03647488


Locations
Layout table for location information
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
France
Novartis Investigative Site
Grenoble, France, 38043
Novartis Investigative Site
LILLE Cédex, France, 59037
Germany
Novartis Investigative Site
Koeln, Germany, 50937
Israel
Novartis Investigative Site
Tel Aviv, Israel, 6423906
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Madrid, Spain, 28009
Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] July 16, 2018
Statistical Analysis Plan  [PDF] October 5, 2020

Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03647488    
Other Study ID Numbers: CINC280D2201
2018-001420-19 ( EudraCT Number )
First Posted: August 27, 2018    Key Record Dates
Results First Posted: October 25, 2021
Last Update Posted: January 24, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Spartalizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immune Checkpoint Inhibitors