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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 : April 25, 2024
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Description
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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: Trametinib Drug: RMC-4630 Drug: Afatinib Drug: Pembrolizumab Drug: Panitumumab Drug: Carboplatin, pemetrexed, docetaxel, paclitaxel Drug: Atezolizumab Drug: Palbociclib Drug: MVASI® (bevacizumab-awwb) Drug: TNO155 Drug: Intravenous (IV) Chemotherapy (Regimen 1) Drug: IV Chemotherapy (Regimen 2) Drug: BI 1701963 Drug: AMG 404 Drug: Everolimus Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1126 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : December 17, 2019
Estimated Primary Completion Date : December 20, 2026
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Sotorasib

Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Trametinib
Trametinib administered orally as a tablet.

Drug: Panitumumab
Panitumumab administered as an intravenous (IV) infusion.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: RMC-4630
RMC-4630 administered orally as a capsule.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Afatinib
afatinib administered orally as a tablet.
Experimental: Sotorasib + panitumumab +/- chemotherapy

Experimental: Sotorasib + panitumumab +/- chemotherapy 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: Panitumumab
Panitumumab administered as an intravenous (IV) infusion.

Drug: Intravenous (IV) Chemotherapy (Regimen 1)
Chemotherapy combination of leucovorin administered as an IV injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Atezolizumab
Atezolizumab administered as an intravenous (IV) injection.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Pembrolizumab
pembrolizumab administered as an intravenous (IV) infusion.

Drug: Carboplatin, pemetrexed, docetaxel, paclitaxel
Carboplatin, pemetrexed, docetaxel 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 + 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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Palbociclib
Palbociclib administered orally as a tablet.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Pembrolizumab
pembrolizumab administered as an intravenous (IV) infusion.
Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy

Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy 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: MVASI® (bevacizumab-awwb)
MVASI® (bevacizumab-awwb) administered as an intravenous (IV) infusion.

Drug: Intravenous (IV) Chemotherapy (Regimen 1)
Chemotherapy combination of leucovorin administered as an 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: IV Chemotherapy (Regimen 2)
IV chemotherapy combination of leucovorin administered as an IV injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: TNO155
TNO155 administered orally as a capsule.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: BI 1701963
BI 1701963 administered orally
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
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: AMG 404
AMG 404 administered as an intravenous (IV) infusion.
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.
 Drug: Sotorasib
Sotorasib administered orally as a tablet.

Drug: Everolimus
Everolimus administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 12 Months ]
  2. Phase 1b: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  3. Phase 1b: Number of Participants with Treatment-related Adverse Events [ Time Frame: 12 Months ]
  4. Phase 1b: Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: 12 Months ]
  5. Phase 1b: Number of Participants with Clinically Significant Changes in ECG Measurements [ Time Frame: 12 Months ]
  6. Phase 2: Objective Response Rate [ Time Frame: 12 Months ]
  7. Phase 1b: Number of Participants with Clinically Significant Changes in Laboratory Test Values [ Time Frame: 12 Months ]

Secondary Outcome Measures :
  1. Phase 1b: Maximum Plasma Concentration (Cmax) [ Time Frame: 12 Months ]
  2. Phase 1b: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: 12 Months ]
  3. Phase 1b: Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 12 Months ]
  4. Phase 1b: Objective Response Rate [ Time Frame: 12 Months ]
  5. Phase 1b: Disease Control Rate [ Time Frame: 12 Months ]
  6. Phase 1b: Duration of Response [ Time Frame: 12 Months ]
  7. Phase 1b: Progression-free Survival [ Time Frame: 12 Months ]
  8. Phase 1b: Duration of Stable Disease [ Time Frame: 12 Months ]
  9. Phase 1b: Time to Response [ Time Frame: 12 Months ]
  10. Phase 1b: Overall Survival [ Time Frame: 12 Months ]
  11. Phase 1b: Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels [ Time Frame: 12 Months ]
  12. 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).

  13. 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).

  14. 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).

  15. Phase 1b: Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy [ Time Frame: 12 Months ]
  16. 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)

  17. Phase 1b: Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS) [ Time Frame: 12 Months ]
    Non-intracranial PFS assessed per RECIST 1.1.

  18. Phase 1b: Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS) [ Time Frame: 12 Months ]
    Overall PFS assessed per RECIST 1.1 and RANO-BM.

  19. Phase 1b: Sotorasib + TNO155 Only: Best Overall Response [ Time Frame: 12 Months ]
  20. Phase 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  21. Phase 2: Number of Participants with Grade ≥3 Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  22. Phase 2: Maximum Plasma Concentration (Cmax) [ Time Frame: 12 Months ]
  23. Phase 2: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: 12 Months ]
  24. Phase 2: Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 12 Months ]
  25. Phase 2: Disease Control Rate [ Time Frame: 12 Months ]
  26. Phase 2: Duration of Response [ Time Frame: 12 Months ]
  27. Phase 2: Progression-free Survival [ Time Frame: 12 Months ]
  28. Phase 2: Time to Response [ Time Frame: 12 Months ]
  29. Phase 2: Overall Survival [ Time Frame: 12 Months ]
  30. Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 12 Months ]
  31. Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 Months ]
  32. Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events [ Time Frame: 12 Months ]
  33. Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: 12 Months ]
  34. Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements [ Time Frame: 12 Months ]
  35. Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values [ Time Frame: 12 Months ]

Eligibility Criteria
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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 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.
Contacts and Locations
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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
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
More Information
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Additional Information:

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04185883    
Other Study ID Numbers: 20190135
2023-506794-35 ( Other Identifier: CTIS )
First Posted: December 4, 2019    Key Record Dates
Last Update Posted: April 25, 2024
Last Verified: April 2024
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
Docetaxel
Bevacizumab
Carboplatin
Pembrolizumab
Pemetrexed
Everolimus
Atezolizumab
Palbociclib
Panitumumab
Trametinib
Afatinib
 Sotorasib
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immune Checkpoint Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists