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AMG 510 (pINN) Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

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ClinicalTrials.gov Identifier: NCT04185883
Recruitment Status : Recruiting
First Posted : December 4, 2019
Last Update Posted : March 1, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Kirsten Rat Sarcoma (KRAS) pG12C Mutation Drug: Sotorasib Drug: PD1 inhibitor Drug: MEK inhibitor Drug: SHP2 allosteric inhibitor Drug: Pan-ErbB tyrosine kinase inhibitor Drug: PD-L1 inhibitor Drug: EGFR inhibitor Drug: Chemotherapeutic regimen Drug: PD-1 inhibitor Drug: mTOR inhibitor Drug: CDK inhibitor Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1003 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 510 (pINN) Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
Actual Study Start Date : December 17, 2019
Estimated Primary Completion Date : May 30, 2023
Estimated Study Completion Date : July 4, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sotorasib + MEK inhibitor

Experimental: Sotorasib + MEK inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: MEK inhibitor
MEK inhibitor administered orally as a tablet.

Experimental: Sotorasib + PD1 inhibitor

Experimental: Sotoasib + PD1 inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: PD1 inhibitor
PD1 inhibitor administered as an intravenous (IV) infusion.

Experimental: Sotorasib + SHP2 allosteric inhibitor

Experimental: Sotorasib + SHP2 allosteric inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: SHP2 allosteric inhibitor
SHP2 allosteric inhibitor administered orally as a capsule.

Experimental: Sotorasib + Pan-ErbB tyrosine kinase inhibitor

Experimental:Sotorasib + pan-ErbB tyrosine kinase inhibitor Dose Exploration and Dose Expansion

  • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Pan-ErbB tyrosine kinase inhibitor
Pan-ErbB tyrosine kinase inhibitor administered orally as a tablet.

Experimental: Sotorasib + PD-L1 inhibitor

Experimental: Sotorasib + PD-L1 inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: PD-L1 inhibitor
PD-L1 inhibitor administered as an intravenous (IV) infusion.

Experimental: Sotorasib + EGFR inhibitor +/- Chemotherapeutic regimen

Experimental: Sotorasib + EGFR inhibitor +/- Chemotherapeutic regimen 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: EGFR inhibitor
EGFR inhibitor administered as an intravenous (IV) infusion.

Drug: Chemotherapeutic regimen
Chemotherapeutic regimen administered as an intravenous (IV) infusion.

Experimental: Sotorasib + PD-1 inhibitor

Sotorasib + PD-1 inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: PD-1 inhibitor
PD-1 inhibitor administered as an intravenous (IV) injection.

Experimental: Sotorasib + Chemotherapeutic regimen

Experimental: Sotorasib + Chemotherapeutic regimen 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Chemotherapeutic regimen
Chemotherapeutic regimen administered as an intravenous (IV) infusion.

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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Experimental: Sotorasib + CDK inhibitor

Experimental: Sotorasib + CDK inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: CDK inhibitor
CDK inhibitor administered orally as a tablet.

Experimental: Sotorasib + mTOR inhibitor

Experimental: Sotorasib + mTOR inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: mTOR inhibitor
mTOR inhibitor administered orally.

Experimental: Sotorasib + MEK inhibitor + EGFR inhibitor

Experimental: Sotorasib + MEK inhibitor + EGFR inhibitor 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.
Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: MEK inhibitor
MEK inhibitor administered orally as a tablet.

Drug: EGFR inhibitor
EGFR inhibitor administered as an intravenous (IV) infusion.




Primary Outcome Measures :
  1. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 12 months ]
  2. Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 months ]
  3. Number of Participants with Treatment-related Adverse Events [ Time Frame: 12 months ]
  4. Number of Participants with Clinically Significant Changes in Vital Signs. [ Time Frame: 12 months ]
  5. Number of Participants with Clinically Significant Changes in ECG Measurement [ Time Frame: 12 months ]
  6. Number of participants with clinically significant changes in laboratory test values [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) [ Time Frame: 12 months ]
  2. Time to Maximum Plasma Concentration (Tmax) [ Time Frame: 12 months ]
  3. Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 12 months ]
  4. Disease Control Rate [ Time Frame: 12 months ]
  5. Duration of Response [ Time Frame: 12 Months ]
  6. Progression-free Survival [ Time Frame: 12 months ]
  7. Duration of Stable Disease [ Time Frame: 12 Months ]
  8. Objective Response Rate [ Time Frame: 12 months ]
  9. Time to Response [ Time Frame: 12 Months ]
  10. Overall Survival [ Time Frame: 12 Months ]
  11. 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).

  12. 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).

  13. 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).

  14. Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy [ Time Frame: 12 Months ]
  15. Sotorasib Monotherapy Only: Central Nervous System Progression-free Survival [ Time Frame: 12 Months ]
  16. Sotorasib Monotherapy Only: Non-Central Nervous System Progression-free Survival [ Time Frame: 12 Months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04185883


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, California
Research Site Recruiting
Duarte, California, United States, 91010
Research Site Recruiting
La Jolla, California, United States, 92093
Research Site Recruiting
Loma Linda, California, United States, 92354
Research Site Recruiting
Sacramento, California, United States, 95817
Research Site Recruiting
Santa Monica, California, United States, 90404
United States, Connecticut
Research Site Recruiting
New Haven, Connecticut, United States, 06473
Research Site Recruiting
Norwalk, Connecticut, United States, 06856
United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site Recruiting
Chicago, Illinois, United States, 60637
United States, Indiana
Research Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Maryland
Research Site Recruiting
Baltimore, Maryland, United States, 21287
United States, Michigan
Research Site Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site Recruiting
New York, New York, United States, 10022
Research Site Recruiting
New York, New York, United States, 10032
United States, North Carolina
Research Site Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45219
Research Site Recruiting
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Research Site Recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Research Site Recruiting
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site Recruiting
Dallas, Texas, United States, 75230
Research Site Recruiting
Houston, Texas, United States, 77030
United States, Utah
Research Site Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04185883    
Other Study ID Numbers: 20190135
First Posted: December 4, 2019    Key Record Dates
Last Update Posted: March 1, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs