KRAS p.G12C Mutant Advanced Solid Tumors
Conditions
Brief summary
Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.
Interventions
DRUGsotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
DRUGAnti PD-1/L1
Administered as an intravenous (IV) infusion
DRUGMidazolam
Administered as an oral hydrochloride (HCI) syrup
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary: Number of subjects with treatment-emergent adverse events | 24 Months | Treatment-emergent adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison |
| Primary: Number of subjects with treatment-related adverse events | 24 Months | Treatment-related adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Number of subjects with grade ≥3 treatment-emergent adverse events | 24 Months | Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison |
| Primary: Number of subjects with serious adverse events | 24 Months | Serious adverse events will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison |
| Primary: Number of subjects with adverse events of interest | 24 Months | Adverse events of interest will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison |
| Primary: Number of subjects with clinically significant changes in vital signs | Baseline to 24 Months | Vital signs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Number of subjects with clinically significant changes in physical examination results | Baseline to 24 Months | Physical examinations will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 |
| Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs) | Baseline to 24 Months | ECGs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Number of subjects with clinically significant changes in clinical laboratory values | Baseline to 24 Months | Abnormal clinical laboratory values will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Number of subjects with dose-limiting toxicities (DLTs) | 21 Days | DLTs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria | 24 Months | ORR will be a primary outcome measure in the following group: * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy * Phase 2 monotherapy dose comparison |
| Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria | 24 Months | DOR will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Disease control as assessed by RECIST 1.1 criteria | 24 Months | Disease control will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria | 24 Months | Duration of SD will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria | 24 Months | TTR will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary: Plasma concentration (Cmax) of sotorasib | 15 Weeks | Cmax will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison |
| Secondary: Plasma concentration (Cmax) of midazolam | 16 Days | Cmax of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: Time to achieve Cmax (Tmax) of sotorasib | 15 Weeks | Tmax will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib | 15 Weeks | AUC will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison |
| Secondary: Area under the plasma concentration-time curve (AUC) of midazolam | 16 Days | AUC of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: Clearance of midazolam from the plasma | 16 Days | Clearance of midazolam from the plasma will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: Terminal half-life (t1/2) of midazolam | 16 Days | t1/2 of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria | 24 Months | ORR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 |
| Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria | 24 Months | DOR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison |
| Secondary: Disease control as assessed by RECIST 1.1 criteria | 24 Months | DOR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison |
| Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria | 24 Months | PFS will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria | 24 Months | Duration of SD will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 |
| Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria | Baseline to 24 Months | Depth of response will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria | 24 Months | DOR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison |
| Secondary: Overall survival (OS) | 24 Months | OS will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison * Phase 1 monotherapy treatment naïve advanced NSCLC |
| Secondary: sotorasib exposure and QTc interval relationship | 24 Months | sotorasib exposure and QTc interval relationship will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy |
| Secondary: Progression-free survival (PFS) at 6 months | 6 Months | PFS at 6 months will be a secondary outcome measure for the following group: \- Phase 2 monotherapy |
| Secondary: Progression-free survival (PFS) at 12 months | 12 Months | PFS at 12 months will be a secondary outcome measure for the following group: \- Phase 2 monotherapy |
| Secondary: Overall survival (OS) at 12 months | 12 Months | OS at 12 months will be a secondary outcome measure for the following group: \- Phase 2 monotherapy |
| Secondary: Number of subjects with treatment-emergent adverse events | 24 Months | Treatment-emergent adverse events will be a secondary outcome measure for the following group: \- Phase 2 monotherapy |
| Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events | 24 Months | Grade ≥3 treatment-emergent adverse events will be a secondary outcome measure for the following group: \- Phase 2 monotherapy |
| Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30 | 24 Months | Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| 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) | 24 Months | Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| 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 | 24 Months | Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS) | 24 Months | Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| 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 | 24 Months | Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30 | 24 Months | Treament related symptoms and impact on the subject will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| 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) | 24 Months | Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| 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) | 24 Months | Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
| Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30 | Baseline to 24 Months | Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: \- Phase 2 monotherapy dose comparison |
Countries
Australia, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Hungary, Japan, Portugal, Romania, South Korea, Spain, Switzerland, United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed