Phase 1/2 study to assess mono and combination therapy with AMG 510 in patients with mutated advanced solid tumors

Australia, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Hungary, Japan, Korea, Republic of, Portugal, Romania, Spain, Switzerland, United States (ICTRP)

Identifiant de l'essai ICTRP
NCT03600883 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 510 Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and AMG 510 Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreak 100) (BASEC)

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

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

Maladie en cours d'investigation
KRAS p.G12C Mutant Advanced Solid Tumors (ICTRP)

Intervention étudiée
Drug: sotorasibDrug: Anti PD-1/L1Drug: Midazolam (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Critères d'inclusion/exclusion
Inclusion Criteria:

- Men or women greater than or equal to 18 years old.

- Pathologically documented, locally-advanced or metastatic malignancy with, KRAS
p.G12C mutation identified through molecular testing.

Exclusion Criteria

- Active brain metastases from non-brain tumors.

- Myocardial infarction within 6 months of study day 1.

- Gastrointestinal (GI) tract disease causing the inability to take oral medication. (ICTRP)

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Critères d'évaluation principaux et secondaires
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: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria;Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria (ICTRP)

Secondary: Plasma concentration (Cmax) of sotorasib;Secondary: Plasma concentration (Cmax) of midazolam;Secondary: Time to achieve Cmax (Tmax) of sotorasib;Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib;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: sotorasib 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 (ICTRP)

Date d'enregistrement
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Inclusion du premier participant
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Sponsors secondaires
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Contacts supplémentaires
MD, Amgen (ICTRP)

ID secondaires
20170543 (ICTRP)

Résultats-Données individuelles des participants
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Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT03600883 (ICTRP)