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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04185883




Registration number
NCT04185883
Ethics application status
Date submitted
3/12/2019
Date registered
4/12/2019

Titles & IDs
Public title
Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
Scientific title
A Phase 1b, 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)
Secondary ID [1] 0 0
2023-506794-35
Secondary ID [2] 0 0
20190135
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Kirsten Rat Sarcoma (KRAS) pG12C Mutation 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Sotorasib
Treatment: Drugs - Trametinib
Treatment: Drugs - RMC-4630
Treatment: Drugs - Afatinib
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Panitumumab
Treatment: Drugs - Carboplatin, pemetrexed, docetaxel, paclitaxel
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Palbociclib
Treatment: Drugs - MVASI® (bevacizumab-awwb)
Treatment: Drugs - TNO155
Treatment: Drugs - IV Chemotherapy (Regimen 1)
Treatment: Drugs - IV Chemotherapy (Regimen 2)
Treatment: Drugs - BI 1701963
Treatment: Drugs - AMG 404
Treatment: Drugs - Everolimus

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.


Treatment: Drugs: Sotorasib
Sotorasib administered orally as a tablet.

Treatment: Drugs: Trametinib
Trametinib administered orally as a tablet.

Treatment: Drugs: RMC-4630
RMC-4630 administered orally as a capsule.

Treatment: Drugs: Afatinib
afatinib administered orally as a tablet.

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

Treatment: Drugs: Panitumumab
Panitumumab administered as an IV infusion.

Treatment: Drugs: Carboplatin, pemetrexed, docetaxel, paclitaxel
Carboplatin, pemetrexed, docetaxel administered as an IV infusion.

Treatment: Drugs: Atezolizumab
Atezolizumab administered as an IV injection.

Treatment: Drugs: Palbociclib
Palbociclib administered orally as a tablet.

Treatment: Drugs: MVASI® (bevacizumab-awwb)
MVASI® (bevacizumab-awwb) administered as an IV infusion.

Treatment: Drugs: TNO155
TNO155 administered orally as a capsule.

Treatment: Drugs: 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.

Treatment: Drugs: IV Chemotherapy (Regimen 2)
IV chemotherapy combination of leucovorin administered as an IV injection, 5-FU administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.

Treatment: Drugs: BI 1701963
BI 1701963 administered orally

Treatment: Drugs: AMG 404
AMG 404 administered as an IV infusion.

Treatment: Drugs: Everolimus
Everolimus administered orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
12 Months
Primary outcome [2] 0 0
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
12 Months
Primary outcome [3] 0 0
Number of Participants with Treatment-related Adverse Events
Timepoint [3] 0 0
12 Months
Primary outcome [4] 0 0
Number of Participants with Clinically Significant Changes in Vital Signs
Timepoint [4] 0 0
12 Months
Primary outcome [5] 0 0
Number of Participants with Clinically Significant Changes in ECG Measurements
Timepoint [5] 0 0
12 Months
Primary outcome [6] 0 0
Number of Participants with Clinically Significant Changes in Laboratory Test Values
Timepoint [6] 0 0
12 Months
Secondary outcome [1] 0 0
Maximum Plasma Concentration (Cmax)
Timepoint [1] 0 0
12 Months
Secondary outcome [2] 0 0
Time to Maximum Plasma Concentration (Tmax)
Timepoint [2] 0 0
12 Months
Secondary outcome [3] 0 0
Area Under the Plasma Concentration-time Curve (AUC)
Timepoint [3] 0 0
12 Months
Secondary outcome [4] 0 0
Objective Response Rate
Timepoint [4] 0 0
12 Months
Secondary outcome [5] 0 0
Disease Control Rate
Timepoint [5] 0 0
12 Months
Secondary outcome [6] 0 0
Duration of Response
Timepoint [6] 0 0
12 Months
Secondary outcome [7] 0 0
Progression-free Survival
Timepoint [7] 0 0
12 Months
Secondary outcome [8] 0 0
Duration of Stable Disease
Timepoint [8] 0 0
12 Months
Secondary outcome [9] 0 0
Time to Response
Timepoint [9] 0 0
12 Months
Secondary outcome [10] 0 0
Overall Survival
Timepoint [10] 0 0
12 Months
Secondary outcome [11] 0 0
Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels
Timepoint [11] 0 0
12 Months
Secondary outcome [12] 0 0
Sotorasib Monotherapy Only: Intracranial Objective Response Rate
Timepoint [12] 0 0
12 Months
Secondary outcome [13] 0 0
Sotorasib Monotherapy Only: Intracranial Disease Control Rate
Timepoint [13] 0 0
12 Months
Secondary outcome [14] 0 0
Sotorasib Monotherapy Only: Intracranial Duration of Response
Timepoint [14] 0 0
12 Months
Secondary outcome [15] 0 0
Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy
Timepoint [15] 0 0
12 Months
Secondary outcome [16] 0 0
Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS)
Timepoint [16] 0 0
12 Months
Secondary outcome [17] 0 0
Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS)
Timepoint [17] 0 0
12 Months
Secondary outcome [18] 0 0
Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS)
Timepoint [18] 0 0
12 Months
Secondary outcome [19] 0 0
Sotorasib + TNO155 Only: Best Overall Response
Timepoint [19] 0 0
12 Months
Secondary outcome [20] 0 0
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [20] 0 0
12 Months
Secondary outcome [21] 0 0
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Timepoint [21] 0 0
12 Months
Secondary outcome [22] 0 0
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events
Timepoint [22] 0 0
12 Months
Secondary outcome [23] 0 0
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs
Timepoint [23] 0 0
12 Months
Secondary outcome [24] 0 0
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements
Timepoint [24] 0 0
12 Months
Secondary outcome [25] 0 0
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values
Timepoint [25] 0 0
12 Months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
13/03/2028
Actual
Sample size
Target
1200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Nepean Cancer Centre - Kingswood
Recruitment hospital [2] 0 0
GenesisCare -North Shore Oncology - St Leonards
Recruitment hospital [3] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [5] 0 0
St John of God Healthcare - Subiaco
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5011 - Woodville South
Recruitment postcode(s) [5] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
South Dakota
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
Austria
State/province [25] 0 0
Graz
Country [26] 0 0
Austria
State/province [26] 0 0
Salzburg
Country [27] 0 0
Belgium
State/province [27] 0 0
Bruxelles
Country [28] 0 0
Belgium
State/province [28] 0 0
Edegem
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Dresden
Country [32] 0 0
Germany
State/province [32] 0 0
Essen
Country [33] 0 0
Germany
State/province [33] 0 0
Koeln
Country [34] 0 0
Italy
State/province [34] 0 0
Milano
Country [35] 0 0
Italy
State/province [35] 0 0
Pisa
Country [36] 0 0
Italy
State/province [36] 0 0
Verona
Country [37] 0 0
Japan
State/province [37] 0 0
Aichi
Country [38] 0 0
Japan
State/province [38] 0 0
Chiba
Country [39] 0 0
Japan
State/province [39] 0 0
Tokyo
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Seoul
Country [41] 0 0
Netherlands
State/province [41] 0 0
Utrecht
Country [42] 0 0
Spain
State/province [42] 0 0
Cataluña
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid
Country [44] 0 0
Taiwan
State/province [44] 0 0
Tainan
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taoyuan
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04185883