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

Advanced Solid Tumors Clinical Trial

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04185883
• Other study ID #: 20190135
• Secondary ID: 2023-506794-35
• Status: Recruiting
• Phase: Phase 1
• Start date: December 17, 2019
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 31, 2027
• Est. primary completion date: December 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Kirsten Rat Sarcoma (KRAS) pG12C Mutation
• Neoplasms
• Sarcoma

Intervention

Drug:
• Sotorasib
Sotorasib administered orally as a tablet.
• Trametinib
Trametinib administered orally as a tablet.
• RMC-4630
RMC-4630 administered orally as a capsule.
• Afatinib
afatinib administered orally as a tablet.
• Pembrolizumab
pembrolizumab administered as an intravenous (IV) infusion.
• Panitumumab
Panitumumab administered as an IV infusion.
• Carboplatin, pemetrexed, docetaxel, paclitaxel
Carboplatin, pemetrexed, docetaxel administered as an IV infusion.
• Atezolizumab
Atezolizumab administered as an IV injection.
• Palbociclib
Palbociclib administered orally as a tablet.
• MVASI® (bevacizumab-awwb)
MVASI® (bevacizumab-awwb) administered as an IV infusion.
• TNO155
TNO155 administered orally as a capsule.
• 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.
• 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.
• BI 1701963
BI 1701963 administered orally
• AMG 404
AMG 404 administered as an IV infusion.
• Everolimus
Everolimus administered orally.

Locations

Country	Name	City	State
Australia	Nepean Cancer Centre	Kingswood	New South Wales
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
Australia	GenesisCare -North Shore Oncology	St Leonards	New South Wales
Australia	St John of God Healthcare	Subiaco	Western Australia
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Austria	Medizinische Universitaet Graz	Graz
Austria	Landeskrankenhaus Salzburg	Salzburg
Belgium	Universite Catholique de Louvain Cliniques Universitaires Saint Luc	Bruxelles
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Canada	CHU de Quebec Hopital de l Enfant Jesus	Quebec
Germany	Charite Universitaetsmedizin Berlin, Campus Virchow	Berlin
Germany	Universitaetsklinikum Dresden	Dresden
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitatsklinikum Koln	Koeln
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Centro Ricerche Cliniche Di Verona Societa responsabilita limitata	Verona
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo
Japan	Aichi Cancer Center	Nagoya-shi	Aichi
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St Marys Hospital	Seoul
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals	Hospitalet de Llobregat	Cataluña
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation	Taoyuan
United Kingdom	Sarah Cannon Research Institute UK	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers Denver Midtown	Denver	Colorado
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Oncology Consultants	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	University of Southern California, Norris Comprehensive Cancer Center	Los Angeles	California
United States	Henry Joyce Cancer Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Memorial Cancer Institute	Pembroke Pines	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center Cancer Pavillion	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	Washington University	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of California at SF	San Francisco	California
United States	University of California Los Angeles	Santa Monica	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Gibbs Cancer Center and Research Institute - Spartanburg	Spartanburg	South Carolina
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	United States Oncology Regulatory Affairs Corporate Office	The Woodlands	Texas
United States	US Oncology Research Investigational Products Center	The Woodlands	Texas
United States	Arizona Oncology Associates Professional Corporation	Tucson	Arizona
United States	Texas Oncology Northeast Texas	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

Kuboki Y, Fakih M, Strickler J, Yaeger R, Masuishi T, Kim EJ, Bestvina CM, Kopetz S, Falchook GS, Langer C, Krauss J, Puri S, Cardona P, Chan E, Varrieur T, Mukundan L, Anderson A, Tran Q, Hong DS. Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial. Nat Med. 2024 Jan;30(1):265-270. doi: 10.1038/s41591-023-02717-6. Epub 2024 Jan 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose Limiting Toxicities (DLTs)		12 Months
Primary	Number of Participants with Treatment-emergent Adverse Events (TEAEs)		12 Months
Primary	Number of Participants with Treatment-related Adverse Events		12 Months
Primary	Number of Participants with Clinically Significant Changes in Vital Signs		12 Months
Primary	Number of Participants with Clinically Significant Changes in ECG Measurements		12 Months
Primary	Number of Participants with Clinically Significant Changes in Laboratory Test Values		12 Months
Secondary	Maximum Plasma Concentration (Cmax)		12 Months
Secondary	Time to Maximum Plasma Concentration (Tmax)		12 Months
Secondary	Area Under the Plasma Concentration-time Curve (AUC)		12 Months
Secondary	Objective Response Rate		12 Months
Secondary	Disease Control Rate		12 Months
Secondary	Duration of Response		12 Months
Secondary	Progression-free Survival		12 Months
Secondary	Duration of Stable Disease		12 Months
Secondary	Time to Response		12 Months
Secondary	Overall Survival		12 Months
Secondary	Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels		12 Months
Secondary	Sotorasib Monotherapy Only: Intracranial Objective Response Rate	Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).	12 Months
Secondary	Sotorasib Monotherapy Only: Intracranial Disease Control Rate	Intracranial disease control rate assessed per RANO-BM.	12 Months
Secondary	Sotorasib Monotherapy Only: Intracranial Duration of Response	Intracranial duration of response assessed per RANO-BM.	12 Months
Secondary	Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy		12 Months
Secondary	Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS)	Intracranial PFS assessed per RANO-BM.	12 Months
Secondary	Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS)	Non-intracranial PFS assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.	12 Months
Secondary	Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS)	Overall PFS assessed per RECIST 1.1 and RANO-BM.	12 Months
Secondary	Sotorasib + TNO155 Only: Best Overall Response		12 Months
Secondary	Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs)		12 Months
Secondary	Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		12 Months
Secondary	Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events		12 Months
Secondary	Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs		12 Months
Secondary	Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements		12 Months
Secondary	Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values		12 Months

External Links

•   AmgenTrials clinical trials website