Clinical trial NCT03647488: Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-27
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Run-in part was single group. Randomized part (parallel design) was not opened.
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From the day of the first dose of study medication up to 56 days
measure: Run-in Part: Percentage of Participants With Adverse Events (AEs)
timeFrame: 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
measure: Run-in Part: Percentage of Participants With at Least One Dose Reduction.
timeFrame: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
measure: Run-in Part: Percentage of Participants With at Least One Dose Interruption
timeFrame: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
measure: Run-in Part: Relative Dose Intensity Received by Participants
timeFrame: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
measure: Randomized Part: Overall Survival (OS)
timeFrame: 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:
measure: Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment
timeFrame: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)
measure: Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment
timeFrame: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)
measure: Progression Free Survival (PFS)
timeFrame: From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part)
measure: Time to Response (TTR) Based on RECIST 1.1 and as Per Investigator Assessment
timeFrame: From start of treatment to the first documented response of either complete response or partial response, assessed up to 68 weeks (run-in part)
measure: Duration of Response (DOR) Based on RECIST 1.1 and as Per Investigator Assessment
timeFrame: From first documented response (CR or PR) to first documented progression or death, whichever came first, assessed up to 68 weeks (run-in part)
measure: AUClast of Capmatinib
timeFrame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
measure: AUCtau of Capmatinib
timeFrame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
measure: Maximum Plasma Concentration (Cmax) of Capmatinib
timeFrame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
measure: Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib
timeFrame: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
measure: AUClast of Spartlizumab
timeFrame: 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
measure: AUCtau of Spartlizumab
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Spartlizumab
timeFrame: 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
measure: Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab
timeFrame: 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
measure: Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline
timeFrame: Cycle 1 Day 1 at predose. Each Cycle is 28 days
measure: Spartalizumab ADA Incidence On-treatment
timeFrame: 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
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: LILLE Cédex
country: France
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
References: