Clinical trial NCT04323436: Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations
Official title: A Double-blind, Placebo Controlled, Randomized, Phase II Study Evaluating the Efficacy and Safety of Capmatinib and Spartalizumab vs Capmatinib and Placebo as 1st Line Treatment for Advanced NSCLC Patients With MET exon14 Skipping Mutations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: capmatinib
spartalizumab
MET mutation
EGFR wild-type
ALK negative mutation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Run-in part: single arm, open-label.

Randomized part: two-arms parallel assignment, double-blinded, placebo control
Primary purpose: TREATMENT

Brief summary: A double-blind, placebo controlled, randomized, phase II study evaluating the efficacy and safety of capmatinib (INC280) and spartalizumab (PDR001) combination therapy versus capmatinib and placebo as first line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping (METΔex14) mutations

Detailed description: The purpose of this study was to evaluate the efficacy and safety of capmatinib in combination with spartalizumab in treatment naive patients with EGFR wild-type, ALK rearrangement negative advanced NSCLC, harboring METΔex14 mutations.

A run-in part (Part 1) was conducted to determine the anti-tumor activity and safety of capmatinib in combination with spartalizumab. Upon review of safety data and confirmation of anti-tumor activity in Part 1, the randomized part (Part 2) was planned to be initiated to compare the efficacy and safety of capmatinib plus spartalizumab to capmatinib plus placebo.

Combined treatment of METΔex14 mutated NSCLC with capmatinib and spartalizumab was expected to result in improved efficacy compared to each single agent due to direct targeting of an oncogenic driver (MET) as well as more efficient stimulation of an anti-tumor immune response than with PD-1 blockade alone.

The study enrollment was halted on 28-Jul-2021 per sponsor's decision. The enrollment halt decision was based on lack of tolerability observed in capmatinib and spartalizumab combination treatment in the run-in part (Part 1) of the trial.

Following the study enrollment halt during Part 1 (Run in Part), Part 2 was not initiated.

Immediately following the enrollment halt:

* All ongoing subjects were discontinued from spartalizumab treatment and continue to receive single agent capmatinib
* Enrolled subjects who had not started study treatment were to receive capmatinib single agent treatment from the start

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed locally advanced or metastatic NSCLC which is EGFR wild-type, ALK rearrangement negative and METΔex14 mutated
* No prior systemic therapy for advanced/metastatic disease (neo-adjuvant/adjuvant treatment completed \> 12 months before relapse are permitted)
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* Measurable disease as per RECIST 1.1
* Known PD-L1 tumor expression status (applicable to Randomized part 2 only)

Key Exclusion Criteria:

* Prior treatment with a PD-1/PD-L1 inhibitor, MET inhibitor or HGF inhibitor
* Presence of symptomatic CNS metastases or requiring local CNS-directed therapy (radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry
* Impaired cardiac function or clinically significant cardiac disease
* Presence or history of interstitial lung disease, non-infectious pneumonitis or interstitial pneumonitis, including clinically significant radiation pneumonitis
* History of allogenic bone marrow or solid organ transplant
* Radiotherapy to lung fields ≤ 4 weeks or to any other anatomic site ≤ 2 weeks prior to start of study treatment (palliative radiotherapy for bone lesions is allowed)

Primary outcomes:
measure: Run-in Part: Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1
timeFrame: Up to approximately 2 years and 4 months
measure: Randomized Part: Progression-Free Survival (PFS) by BIRC as Per RECIST 1.1
timeFrame: Up to 6 years
Secondary outcomes:
measure: Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib
timeFrame: From first dose of capmatinib to last dose, up to 2.4 years
measure: Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Spartalizumab
timeFrame: From first dose of spartalizumab to last dose, up to 0.9 years
measure: Run-in Part: Dose Intensity of Capmatinib
timeFrame: From first dose of capmatinib to last dose, up to 2.4 years
measure: Run-in Part: Dose Intensity of Spartalizumab
timeFrame: From first dose of spartalizumab to last dose, up to 0.9 years
measure: Run-in Part: Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1
timeFrame: Up to approximately 2 years and 4 months
measure: Run-in Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
timeFrame: Up to approximately 2 years and 5 months
measure: Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Capmatinib
timeFrame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: Run-in Part: Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib
timeFrame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib
timeFrame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib
timeFrame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: Run-in Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
timeFrame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
measure: Run-in Part: Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab
timeFrame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
measure: Run-in Part: Area Under the Serum Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Spartalizumab
timeFrame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
measure: Run-in Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
timeFrame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
measure: Randomized Part: Overall Survival (OS)
timeFrame: Up to 12 years
measure: Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib and Spartalizumab
timeFrame: Up to 6 years
measure: Randomized Part: Dose Intensity of Capmatinib and Spartalizumab
timeFrame: Up to 6 years
measure: Randomized Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
timeFrame: Up to 6 years
measure: Randomized Part: Disease Control Rate (DCR) by BIRC and Investigator Assessment as Per RECIST 1.1
timeFrame: Up to 6 years
measure: Randomized Part: Overall Response Rate (ORR) by BIRC and Investigator Assessment as Per RECIST 1.1
timeFrame: Up to 6 years
measure: Randomized Part: Duration of Response (DOR) by BIRC and Investigator Assessment as Per RECIST 1.1
timeFrame: Up to 6 years
measure: Randomized Part: Time to Response (TTR) by BIRC and Investigator Assessment as Per RECIST 1.1
timeFrame: Up to 6 years
measure: Randomized Part: Change From Baseline in EORTC QLQ-C30
timeFrame: Up to 6 years
measure: Randomized Part: Change From Baseline in EORTC QLQ-LC13
timeFrame: Up to 6 years
measure: Randomized Part: Change From Baseline in EQ-5D-5L
timeFrame: Up to 6 years
measure: Randomized Part: Time to Definitive 10 Points Deterioration Symptom Scores for Pain in Chest, Coughing and Dyspnea Per QLQ-LC13 Questionnaire
timeFrame: Up to 6 years
measure: Randomized Part: Time to Definitive Deterioration in Global Health Status/QoL, Shortness of Breath and Pain Per EORTC QLQ-C30
timeFrame: Up to 6 years
measure: Randomized Part: Maximum Observed Concentration (Cmax) of Capmatinib and Spartalizumab
timeFrame: Up to 6 years
measure: Randomized Part: Time to Reach Maximum Concentration (Tmax) of Capmatinib and Spartalizumab
timeFrame: Up to 6 years
measure: Randomized Part: Area Under the Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib and Spartalizumab
timeFrame: Up to 6 years
measure: Randomized Part: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib and Spartalizumab
timeFrame: Up to 6 years
measure: Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
timeFrame: Baseline (pre-dose), up to 6 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Liver and Kidney TX
state: Massachusetts
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Lille
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Gerlingen
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Osaka Sayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
Study officials:
References: