Description:
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
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CINC280J12201
- NCT ID:
NCT04323436
Conditions
- Carcinoma, Non-Small-Cell Lung
Interventions
| Drug | Synonyms | Arms |
|---|
| Spartalizumab | PDR001 | Randomized part - Arm 1 spartalizumab |
| Capmatinib | INC280 | Randomized part - Arm 1 spartalizumab |
| spartalizumab placebo | PDR001 placebo | Randomized part - Arm 2 placebo |
Purpose
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 is 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) will be 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) will 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 is 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Run-in part | Experimental | capmatinib in combination with spartalizumab | |
| Randomized part - Arm 1 spartalizumab | Experimental | capmatinib in combination with spartalizumab | |
| Randomized part - Arm 2 placebo | Experimental | capmatinib in combination with placebo | - Capmatinib
- spartalizumab placebo
|
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)
Other inclusion and exclusion criteras may apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Response Rate by Blinded Independent Review Committee (BIRC) as per RECIST 1.1 |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab |
Secondary Outcome Measures
| Measure: | Adverse events (AE) and Serious Adverse events (SAE) incidence |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To assess safety of capmatinib in combination with spartalizumab |
| Measure: | Number of patients with dose interruptions, reductions, and dose intensity |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To assess tolerability of capmatinib in combination with spartalizumab |
| Measure: | Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab |
| Measure: | Efficacy measurements per RECIST 1.1 : Disease Control Rate (DCR) by BIRC and investigator asessment |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab |
| Measure: | Efficacy measurements per RECIST 1.1 : Duration of Response (DOR) by BIRC and investigator assessment |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run in part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab |
| Measure: | Efficacy measurements per RECIST 1.1 : Progression Free Survival (PFS) by BIRC and investigator assessment |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run in part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab |
| Measure: | Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run in part Time to Response (TTR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab |
| Measure: | Overall Survival (OS) |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To assess the overall survival |
| Measure: | Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab |
| Measure: | Change from baseline in EORTC QLQ-C30 questionnaires |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab |
| Measure: | Change from baseline in QLQ-LC13 questionnaires |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab |
| Measure: | Change from baseline in EQ-5D-5L questionnaires |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab |
| Measure: | Pharmacokinetics (PK): Cmax |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Pharmacokinetics (PK): Tmax |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Pharmacokinetics (PK): AUClast |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Pharmacokinetics (PK): AUCtau |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Antidrug antibody (ADA) prevalence on treatment with spartalizumab |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib |
| Measure: | Antidrug antibody (ADA) incidence on treatment with spartalizumab |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | Run-in part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib |
| Measure: | Overall survival (OS) |
| Time Frame: | 12 years |
| Safety Issue: | |
| Description: | Randomized part To compare overall survival of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Adverse events (AE) and Serious Adverse events (SAE) incidence |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To assess safety of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Number of patients with dose interruptions, reductions, and dose intensity |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To assess tolerability of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Efficacy measurements per RECIST 1.1: Progression Free Survival (PFS) by investigator assessment |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Efficacy measurements per RECIST 1.1: Disease Control Rate (DCR) by BIRC and investigator assessment |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Efficacy measurements per RECIST 1.1: Duration of Response (DOR) by BIRC and investigator assessment |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) by BIRC and investigator assessment |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part Time to Response (TTR) To further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Change from baseline in EORTC QLQ-C30 questionnaires |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Change from baseline in EQ-LC13 questionnaires |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Change from baseline in EQ-5D-5L questionnaires |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo |
| Measure: | Pharmacokinetics (PK): Cmax |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Pharmacokinetics (PK): Tmax |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Pharmacokinetics (PK): AUCtau |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Pharmacokinetics (PK): AUClast. |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate the PK of capmatinib and spartalizumab |
| Measure: | Antidrug antibodies (ADA) prevalence at baseline on treatment with spartalizumab |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib |
| Measure: | Antidrug antibodies (ADA) incidence on treatment with spartalizumab |
| Time Frame: | 6 years |
| Safety Issue: | |
| Description: | Randomized part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- capmatinib
- spartalizumab
- MET mutation
- EGFR wild-type
- ALK negative mutation
Last Updated
August 13, 2021
