Etude : CINC280J12201 /



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : CINC280J12201

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Immunothérapie / Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 06/12/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : 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

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : 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.

STUDY ARMS:
- Experimental: Run-in part
capmatinib in combination with spartalizumab

- Experimental: Randomized part - Arm 1 spartalizumab
capmatinib in combination with spartalizumab

- Experimental: Randomized part - Arm 2 placebo
capmatinib in combination with placebo

CURRENT PRIMARY OUTCOME:
- Overall Response Rate by Blinded Independent Review Committee (BIRC) as per RECIST 1.1 [ Time Frame: 4 years ]
Run-in part To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
- Progression Free survival (PFS) by BIRC as per RECIST 1.1 [ Time Frame: 6 years ]
Randomized part To compare the efficacy of capmatinib in combination with spartalizumab versus capmatinib plus placebo

CURRENT SECONDARY OUTCOMES:
Run-in part:
- Adverse events (AE) and Serious Adverse events (SAE) incidence [ Time Frame: 4 years ]
- Number of patients with dose interruptions, reductions, and dose intensity [ Time Frame: 4 years ]
- Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) [ Time Frame: 4 years ]
- Efficacy measurements per RECIST 1.1 : Disease Control Rate (DCR) by BIRC and investigator asessment [ Time Frame: 4 years ]
- Efficacy measurements per RECIST 1.1 : Duration of Response (DOR) by BIRC and investigator assessment [ Time Frame: 4 years ]
- Efficacy measurements per RECIST 1.1 : Progression Free Survival (PFS) by BIRC and investigator assessment [ Time Frame: 4 years ]
- Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment [ Time Frame: 4 years ]
- Overall Survival (OS) [ Time Frame: 4 years ]
- Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire [ Time Frame: 4 years ]
- Change from baseline in EORTC QLQ-C30 questionnaires [ Time Frame: 4 years ]
- Change from baseline in QLQ-LC13 questionnaires [ Time Frame: 4 years ]
- Change from baseline in EQ-5D-5L questionnaires [ Time Frame: 4 years ]
- Pharmacokinetics (PK): Cmax [ Time Frame: 4 years ]
- Pharmacokinetics (PK): Tmax [ Time Frame: 4 years ]
- Pharmacokinetics (PK): AUClast [ Time Frame: 4 years ]
- Pharmacokinetics (PK): AUCtau [ Time Frame: 4 years ]
- Antidrug antibody (ADA) prevalence on treatment with spartalizumab [ Time Frame: 4 years ]
- Antidrug antibody (ADA) incidence on treatment with spartalizumab [ Time Frame: 4 years ]

Randomized part:
- Overall survival (OS) [ Time Frame: 12 years ]
- Adverse events (AE) and Serious Adverse events (SAE) incidence [ Time Frame: 6 years ]
- Number of patients with dose interruptions, reductions, and dose intensity [ Time Frame: 6 years ]
- Efficacy measurements per RECIST 1.1: Progression Free Survival (PFS) by investigator assessment [ Time Frame: 6 years ]
- Efficacy measurements per RECIST 1.1: Disease Control Rate (DCR) by BIRC and investigator assessment [ Time Frame: 6 years ]
- Efficacy measurements per RECIST 1.1: Duration of Response (DOR) by BIRC and investigator assessment [ Time Frame: 6 years ]
- Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) by BIRC and investigator assessment [ Time Frame: 6 years ]
- Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment [ Time Frame: 6 years ]
- Change from baseline in EORTC QLQ-C30 questionnaires [ Time Frame: 6 years ]
- Change from baseline in EQ-LC13 questionnaires [ Time Frame: 6 years ]
- Change from baseline in EQ-5D-5L questionnaires [ Time Frame: 6 years ]
- Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire [ Time Frame: 6 years ]
- Pharmacokinetics (PK): Cmax [ Time Frame: 6 years ]
- Pharmacokinetics (PK): Tmax [ Time Frame: 6 years ]
- Pharmacokinetics (PK): AUCtau [ Time Frame: 6 years ]
- Pharmacokinetics (PK): AUClast. [ Time Frame: 6 years ]
- Antidrug antibodies (ADA) prevalence at baseline on treatment with spartalizumab [ Time Frame: 6 years ]
- Antidrug antibodies (ADA) incidence on treatment with spartalizumab [ Time Frame: 6 years ]

Phase : II

Stade : Localement avancé à Métastatique

1
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 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)

--- Other inclusion and exclusion criterias may apply ---

Critères de non-inclusion : 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 criterias may apply ---
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04323436
Promoteur :
Novartis Pharmaceuticals
Type de sponsor : Industriel
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Alexis Cortot

TEC / ARC / IDE :
Eric Wasielewski
eric.wasielewski@
chru-lille.fr
03.20.44.56.12

Statut de l'essai : CLOS

MAJ : 21/06/2021