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OpenTrials
Completed

NCT Number: NCT03600883

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)

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.

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Key information

Conditions

KRAS p.G12C Mutant Advanced Solid Tumors

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Scientia Clinical Research Ltd, Randwick, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sotorasib

Drug

Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation

Anti PD-1/L1

Drug

Administered as an intravenous (IV) infusion

midazolam

Drug

Administered as an oral hydrochloride (HCI) syrup

Primary outcomes

  1. Primary: Number of subjects with treatment-emergent adverse events

    Time frame: 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

  2. Primary: Number of subjects with treatment-related adverse events

    Time frame: 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

  3. Primary: Number of subjects with grade ≥3 treatment-emergent adverse events

    Time frame: 24 Months

    Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group:

    • Phase 2 monotherapy dose comparison

  4. Primary: Number of subjects with serious adverse events

    Time frame: 24 Months

    Serious adverse events will be a primary outcome measure in the following group:

    • Phase 2 monotherapy dose comparison

  5. Primary: Number of subjects with adverse events of interest

    Time frame: 24 Months

    Adverse events of interest will be a primary outcome measure in the following group:

    • Phase 2 monotherapy dose comparison

  6. Primary: Number of subjects with clinically significant changes in vital signs

    Time frame: 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

  7. Primary: Number of subjects with clinically significant changes in physical examination results

    Time frame: 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

  8. Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)

    Time frame: 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

  9. Primary: Number of subjects with clinically significant changes in clinical laboratory values

    Time frame: 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

  10. Primary: Number of subjects with dose-limiting toxicities (DLTs)

    Time frame: 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

  11. Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria

    Time frame: 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

  12. Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    DOR will be a primary outcome measure in the following group:

    • Phase 1 monotherapy treatment naïve advanced NSCLC

  13. Primary: Disease control as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    Disease control will be a primary outcome measure in the following group:

    • Phase 1 monotherapy treatment naïve advanced NSCLC

  14. Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    Duration of SD will be a primary outcome measure in the following group:

    • Phase 1 monotherapy treatment naïve advanced NSCLC

  15. Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    TTR will be a primary outcome measure in the following group:

    • Phase 1 monotherapy treatment naïve advanced NSCLC

Secondary outcomes

  1. Secondary: Plasma concentration (Cmax) of sotorasib

    Time frame: 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

  2. Secondary: Plasma concentration (Cmax) of midazolam

    Time frame: 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

  3. Secondary: Time to achieve Cmax (Tmax) of sotorasib

    Time frame: 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

  4. Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib

    Time frame: 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

  5. Secondary: Area under the plasma concentration-time curve (AUC) of midazolam

    Time frame: 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

  6. Secondary: Clearance of midazolam from the plasma

    Time frame: 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

  7. Secondary: Terminal half-life (t1/2) of midazolam

    Time frame: 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

  8. Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria

    Time frame: 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

  9. Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria

    Time frame: 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

  10. Secondary: Disease control as assessed by RECIST 1.1 criteria

    Time frame: 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

  11. Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria

    Time frame: 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

  12. Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria

    Time frame: 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

  13. Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria

    Time frame: Baseline to 24 Months

    Depth of response will be a secondary outcome measure for the following group:

    • Phase 2 monotherapy dose comparison

  14. Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria

    Time frame: 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

  15. Secondary: Overall survival (OS)

    Time frame: 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

  16. Secondary: sotorasib exposure and QTc interval relationship

    Time frame: 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

  17. Secondary: Progression-free survival (PFS) at 6 months

    Time frame: 6 Months

    PFS at 6 months will be a secondary outcome measure for the following group:

    • Phase 2 monotherapy

  18. Secondary: Progression-free survival (PFS) at 12 months

    Time frame: 12 Months

    PFS at 12 months will be a secondary outcome measure for the following group:

    • Phase 2 monotherapy

  19. Secondary: Overall survival (OS) at 12 months

    Time frame: 12 Months

    OS at 12 months will be a secondary outcome measure for the following group:

    • Phase 2 monotherapy

  20. Secondary: Number of subjects with treatment-emergent adverse events

    Time frame: 24 Months

    Treatment-emergent adverse events will be a secondary outcome measure for the following group:

    • Phase 2 monotherapy

  21. Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events

    Time frame: 24 Months

    Grade ≥3 treatment-emergent adverse events will be a secondary outcome measure for the following group:

    • Phase 2 monotherapy

  22. Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30

    Time frame: 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

  23. 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)

    Time frame: 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

  24. 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

    Time frame: 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

  25. Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS)

    Time frame: 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

  26. 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

    Time frame: 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

  27. Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30

    Time frame: 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

  28. 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)

    Time frame: 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

  29. 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)

    Time frame: 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

  30. Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study title

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)

Important dates

Study start
2018
Primary completion
2026
Study completion
2026
First posted
Jul 26, 2018
Registry last updated
Jun 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.