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Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04185883
Recruitment Status : Recruiting
First Posted : December 4, 2019
Last Update Posted : May 25, 2023
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE December 3, 2019
First Posted Date  ICMJE December 4, 2019
Last Update Posted Date May 25, 2023
Actual Study Start Date  ICMJE December 17, 2019
Estimated Primary Completion Date July 12, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2021)
  • Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 12 Months ]
  • Phase 1b: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  • Phase 1b: Number of Participants with Treatment-related Adverse Events [ Time Frame: 12 Months ]
  • Phase 1b: Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: 12 Months ]
  • Phase 1b: Number of Participants with Clinically Significant Changes in ECG Measurements [ Time Frame: 12 Months ]
  • Phase 1b: Number of Participants with Clinically Significant Changes in Laboratory Test Values [ Time Frame: 12 Months ]
  • Phase 2: Objective Response Rate [ Time Frame: 12 Months ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 3, 2019)
  • Number of Participants with Abnormal Laboratory Values [ Time Frame: 12 months ]
  • Number of subjects with clinically significant changes in vital signs. [ Time Frame: 12 months ]
  • Number of subjects with changes on ECG. [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2021)
  • Phase 1b: Maximum Plasma Concentration (Cmax) [ Time Frame: 12 Months ]
  • Phase 1b: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: 12 Months ]
  • Phase 1b: Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 12 Months ]
  • Phase 1b: Objective Response Rate [ Time Frame: 12 Months ]
  • Phase 1b: Disease Control Rate [ Time Frame: 12 Months ]
  • Phase 1b: Duration of Response [ Time Frame: 12 Months ]
  • Phase 1b: Progression-free Survival [ Time Frame: 12 Months ]
  • Phase 1b: Duration of Stable Disease [ Time Frame: 12 Months ]
  • Phase 1b: Time to Response [ Time Frame: 12 Months ]
  • Phase 1b: Overall Survival [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib Monotherapy Only: Intracranial Objective Response Rate [ Time Frame: 12 Months ]
    Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
  • Phase 1b: Sotorasib Monotherapy Only: Intracranial Disease Control Rate [ Time Frame: 12 Months ]
    Intracranial disease control rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
  • Phase 1b: Sotorasib Monotherapy Only: Intracranial Duration of Response [ Time Frame: 12 Months ]
    Intracranial duration of response assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
  • Phase 1b: Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS) [ Time Frame: 12 Months ]
    Intracranial PFS assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM)
  • Phase 1b: Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS) [ Time Frame: 12 Months ]
    Non-intracranial PFS assessed per RECIST 1.1.
  • Phase 1b: Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS) [ Time Frame: 12 Months ]
    Overall PFS assessed per RECIST 1.1 and RANO-BM.
  • Phase 1b: Sotorasib + TNO155 Only: Best Overall Response [ Time Frame: 12 Months ]
  • Phase 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  • Phase 2: Number of Participants with Grade ≥3 Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  • Phase 2: Maximum Plasma Concentration (Cmax) [ Time Frame: 12 Months ]
  • Phase 2: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: 12 Months ]
  • Phase 2: Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 12 Months ]
  • Phase 2: Disease Control Rate [ Time Frame: 12 Months ]
  • Phase 2: Duration of Response [ Time Frame: 12 Months ]
  • Phase 2: Progression-free Survival [ Time Frame: 12 Months ]
  • Phase 2: Time to Response [ Time Frame: 12 Months ]
  • Phase 2: Overall Survival [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements [ Time Frame: 12 Months ]
  • Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values [ Time Frame: 12 Months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2019)
  • Maximum Plasma concentration (Cmax) [ Time Frame: 12 months ]
  • Time to maximum plasma concentration (tmax) [ Time Frame: 12 months ]
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: 12 months ]
  • Disease control rate [ Time Frame: 12 months ]
  • Duration of response [ Time Frame: 12 Months ]
  • Progression-free survival [ Time Frame: 12 months ]
  • Duration of stable disease [ Time Frame: 12 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
Official Title  ICMJE A Phase 1b/2, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
Brief Summary To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Kirsten Rat Sarcoma (KRAS) pG12C Mutation
Intervention  ICMJE
  • Drug: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: AMG 404
    AMG 404 administered as an intravenous (IV) infusion.
  • Drug: trametinib
    trametinib administered orally as a tablet.
  • Drug: RMC-4630
    RMC-4630 administered orally as a capsule.
  • Drug: afatinib
    afatinib administered orally as a tablet.
  • Drug: pembrolizumab
    pembrolizumab administered as an intravenous (IV) infusion.
  • Drug: panitumumab
    panitumumab administered as an intravenous (IV) infusion.
  • Drug: carboplatin, pemetrexed, docetaxel, paclitaxel
    carboplatin, pemetrexed, docetaxel administered as an intravenous (IV) infusion.
  • Drug: atezolizumab
    atezolizumab administered as an intravenous (IV) injection.
  • Drug: everolimus
    everolimus administered orally.
  • Drug: palbociclib
    palbociclib administered orally as a tablet.
  • Drug: MVASI® (bevacizumab-awwb)
    MVASI® (bevacizumab-awwb) administered as an intravenous (IV) infusion.
  • Drug: TNO155
    TNO155 administered orally as a capsule.
  • Drug: FOLFIRI
    FOLFIRI chemotherapy combination of leucovorin administered as an intravenous (IV) injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection.
  • Drug: FOLFOX
    FOLFOX chemotherapy combination of leucovorin administered as intravenous (IV) injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.
  • Drug: BI 1701963
    BI 1701963 administered orally
Study Arms  ICMJE
  • Experimental: Sotorasib + trametinib + panitumumab

    Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
    Interventions:
    • Drug: Sotorasib
    • Drug: trametinib
    • Drug: panitumumab
  • Experimental: Sotorasib + AMG 404

    Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
    Interventions:
    • Drug: Sotorasib
    • Drug: AMG 404
  • Experimental: Sotorasib + RMC-4630

    Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.
    Interventions:
    • Drug: Sotorasib
    • Drug: RMC-4630
  • Experimental: Sotorasib + afatinib

    Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
    Interventions:
    • Drug: Sotorasib
    • Drug: afatinib
  • Experimental: Sotorasib + panitumumab +/- FOLFIRI

    Experimental: Sotorasib + panitumumab +/- FOLFIRI Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
    Interventions:
    • Drug: Sotorasib
    • Drug: panitumumab
    • Drug: FOLFIRI
  • Experimental: Sotorasib + atezolizumab

    Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
    Interventions:
    • Drug: Sotorasib
    • Drug: atezolizumab
  • Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab

    Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
    Interventions:
    • Drug: Sotorasib
    • Drug: pembrolizumab
    • Drug: carboplatin, pemetrexed, docetaxel, paclitaxel
  • Experimental: Sotorasib Monotherapy

    Experimental: Sotorasib only Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases.
    Intervention: Drug: Sotorasib
  • Experimental: Sotorasib + palbociclib

    Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.
    Interventions:
    • Drug: Sotorasib
    • Drug: palbociclib
  • Experimental: Sotorasib + everolimus

    Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.
    Interventions:
    • Drug: Sotorasib
    • Drug: everolimus
  • Experimental: Sotorasib + pembrolizumab

    Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer.
    Interventions:
    • Drug: Sotorasib
    • Drug: pembrolizumab
  • Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX

    Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.
    Interventions:
    • Drug: Sotorasib
    • Drug: MVASI® (bevacizumab-awwb)
    • Drug: FOLFIRI
    • Drug: FOLFOX
  • Experimental: Sotorasib + TNO155

    Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
    • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
    Interventions:
    • Drug: Sotorasib
    • Drug: TNO155
  • Experimental: Sotorasib + BI 1701963

    Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion

    • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
    • Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer.
    Interventions:
    • Drug: Sotorasib
    • Drug: BI 1701963
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2022)		 1143
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2019)		 120
Estimated Study Completion Date  ICMJE January 14, 2029
Estimated Primary Completion Date July 12, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.

Exclusion Criteria:

  • Primary brain tumor.
  • Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or leptomeningeal disease from non-brain tumors.
  • Myocardial infarction within 6 months of study day 1.
  • Gastrointestinal (GI) tract disease causing the inability to take oral medication.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04185883
Other Study ID Numbers  ICMJE 20190135
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: http://www.amgen.com/datasharing
Current Responsible Party Amgen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amgen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date May 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP