A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumours With a Specific KRAS Mutation (CodeBreaK 100)

Titre officiel

A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 510 Monotherapy in Subjects With Advanced Solid Tumours With KRAS p.G12C Mutation and AMG 510 Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)

Sommaire:

Évaluer l’innocuité et la tolérabilité d’AMG 510 chez des sujets adultes atteints de tumeurs solides avec mutation du gène KRAS p.G12C à un stade avancé. Estimer la dose maximale tolérée (DMT) et/ou une dose de phase II recommandée (DP2R) chez des sujets adultes atteints de tumeurs solides avec mutation du gène KRAS p.G12C à un stade avancé.

Description de l'essai

Primary Outcome:

• Primary: Number of subjects with treatment-emergent adverse events
• Primary: Number of subjects with treatment-related adverse events
• Primary: Number of subjects with grade ≥3 treatment-emergent adverse events
• Primary: Number of subjects with serious adverse events
• Primary: Number of subjects with adverse events of interest
• Primary: Number of subjects with clinically significant changes in vital signs
• Primary: Number of subjects with clinically significant changes in physical examination results
• Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)
• Primary: Number of subjects with clinically significant changes in clinical laboratory values
• Primary: Number of subjects with dose-limiting toxicities (DLTs)
• Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
• Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
• Primary: Disease control as assessed by RECIST 1.1 criteria
• Primary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
• Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
• Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria

• Secondary: Plasma concentration (Cmax) of AMG 510
• Secondary: Plasma concentration (Cmax) of midazolam
• Secondary: Time to achieve Cmax (Tmax) of AMG 510
• Secondary: Area under the plasma concentration-time curve (AUC) of AMG 510
• Secondary: Area under the plasma concentration-time curve (AUC) of midazolam
• Secondary: Clearance of midazolam from the plasma
• Secondary: Terminal half-life (t1/2) of midazolam
• Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
• Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
• Secondary: Disease control as assessed by RECIST 1.1 criteria
• Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
• Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
• Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria
• Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria
• Secondary: Overall survival (OS)
• Secondary: AMG 510 exposure and QTc interval relationship
• Secondary: Progression-free survival (PFS) at 6 months
• Secondary: Progression-free survival (PFS) at 12 months
• Secondary: Overall survival (OS) at 12 months
• Secondary: Number of subjects with treatment-emergent adverse events
• Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events
• Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13)
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS)
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC
• Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30
• Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library)
• Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G)
• Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30

Voir cet essai sur ClinicalTrials.gov