A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
NCT ID: NCT03600883
Last Updated: 2026-01-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
713 participants
INTERVENTIONAL
2018-08-27
2026-03-31
Brief Summary
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Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Phase 1 Dose Exploration Part 1 monotherapy
Cohorts with food effect and alternative dosing regimens
Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort
sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Phase 1 Dose Expansion Part 2 monotherapy
Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently
sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Phase 1 combination arm with sotorasib and anti PD-1/L1
Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)
sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Anti PD-1/L1
Administered as an intravenous (IV) infusion
Phase 1 monotherapy treatment naive advanced NSCLC
Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days.
sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Midazolam
Administered as an oral hydrochloride (HCI) syrup
Phase 2 monotherapy dose comparison
Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy
sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Phase 1 Does escalation and Expansion monotherapy BID
BID 2L+solid tumors (fed state)
sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Interventions
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sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Anti PD-1/L1
Administered as an intravenous (IV) infusion
Midazolam
Administered as an oral hydrochloride (HCI) syrup
Eligibility Criteria
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Inclusion Criteria
* Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing.
Exclusion Criteria
* Myocardial infarction within 6 months of study day 1.
* Gastrointestinal (GI) tract disease causing the inability to take oral medication.
18 Years
100 Years
ALL
No
Sponsors
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Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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City of Hope National Medical Center
Duarte, California, United States
University of California Los Angeles
Los Angeles, California, United States
University of California at SF
San Francisco, California, United States
Sarcoma Oncology Research Center LLC
Santa Monica, California, United States
Rocky Mountain Cancer Centers
Denver, Colorado, United States
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, United States
Medical Oncology Hematology Consultants Helen F Graham Cancer Center
Newark, Delaware, United States
University of Florida Health
Gainesville, Florida, United States
AdventHealth Orlando Infusion Center
Orlando, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Winship Cancer Institute
Atlanta, Georgia, United States
Indiana University
Indianapolis, Indiana, United States
American Oncology Partners of Maryland, PA
Bethesda, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
Washington University
St Louis, Missouri, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Laura and Isaac Perlmutter Cancer Center at New York University Langone
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Duke University Medical Center, Morris Cancer Clinic
Durham, North Carolina, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Cancer Pavillion
Pittsburgh, Pennsylvania, United States
Gibbs Cancer Center and Research Institute - Spartanburg
Spartanburg, South Carolina, United States
Vanderbilt University Ingram Cancer Center
Nashville, Tennessee, United States
Texas Oncology - Austin Central
Austin, Texas, United States
Texas Oncology - Baylor
Dallas, Texas, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
US Oncology Research Investigational Products Center
Fairfax, Virginia, United States
Virginia Cancer Specialists PC
Fairfax, Virginia, United States
Blue Ridge Cancer Care
Salem, Virginia, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
Scientia Clinical Research Ltd
Randwick, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Peter MacCallum Cancer Centre
Parkville, Victoria, Australia
Medizinische Universitaet Graz
Graz, , Austria
Medizinische Universitaet Innsbruck
Innsbruck, , Austria
Universitaetsklinikum Krems
Krems, , Austria
Universitaetsklinikum Allgemeines Krankenhaus Wien
Vienna, , Austria
Krankenhaus Nord - Klinik Floridsdorf
Vienna, , Austria
Institut Jules Bordet
Brussels, , Belgium
Grand Hopital de Charleroi
Charleroi, , Belgium
Universitair Ziekenhuis Antwerpen
Edegem, , Belgium
Ziekenhuis Oost-Limburg
Genk, , Belgium
Universitair Ziekenhuis Gent
Ghent, , Belgium
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, , Belgium
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
Leuven, , Belgium
Centre Hospitalier Universitaire de Liege
Liège, , Belgium
AZ Delta Campus Rumbeke
Roeselare, , Belgium
Irmandade da Santa Casa de Misericordia de Porto Alegre, Nucleo de Novos Tratamentos em Cancer
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, Brazil
Hospital de Base de Sao Jose do Rio Preto
São José do Rio Preto, São Paulo, Brazil
Sociedade Beneficente de Senhoras Hospital Sirio Libanes
São Paulo, São Paulo, Brazil
Oncologia Rede D´Or
São Paulo, São Paulo, Brazil
Instituto Coi
Rio de Janeiro, , Brazil
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
London Regional Cancer Program, London Health Sciences Centre
London, Ontario, Canada
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
McGill University Health Centre Glen Site
Montreal, Quebec, Canada
Institut Bergonie
Bordeaux, , France
Centre Hospitalier Intercommunal de Créteil
Créteil, , France
Hopital de la Timone
Marseille, , France
Institut Curie
Paris, , France
Institut Claudius Regaud
Toulouse, , France
Gustave Roussy
Villejuif, , France
Universitatsklinikum Koln
Cologne, , Germany
Universitätsklinikum Essen
Essen, , Germany
Klinikum der Universität München Campus Grosshadern
München, , Germany
Henry Dunant Hospital Center
Athens, , Greece
Metropolitan Hospital
Athens, , Greece
University Hospital of Heraklion
Heraklion - Crete, , Greece
Theagenion Cancer Hospital
Thessaloniki, , Greece
Agios Loukas Clinic
Thessaloniki, , Greece
Semmelweis Egyetem
Budapest, , Hungary
Orszagos Koranyi Pulmonologiai Intezet
Budapest, , Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, , Hungary
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
Székesfehérvár, , Hungary
Szent Borbala Korhaz
Tatabánya, , Hungary
Tudogyogyintezet Torokbalint
Törökbálint, , Hungary
Aichi Cancer Center
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East
Kashiwa-shi, Chiba, Japan
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, Japan
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, Japan
St Marianna University Hospital
Kawasaki-shi, Kanagawa, Japan
Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
Yokohama, Kanagawa, Japan
Sendai Kousei Hospital
Sendai, Miyagi, Japan
Niigata Cancer Center Hospital
Niigata, Niigata, Japan
Okayama University Hospital
Okayama, Okayama-ken, Japan
Kansai Medical University Hospital
Hirakata-shi, Osaka, Japan
Osaka International Cancer Institute
Osaka, Osaka, Japan
Shizuoka Cancer Center
Sunto-gun, Shizuoka, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-ku, Tokyo, Japan
Wakayama Medical University Hospital
Wakayama, Wakayama, Japan
Fundacao Champalimaud
Lisbon, , Portugal
Centro Hospitalar Universitario de Lisboa Norte EPE - Hospital Pulido Valente
Lisbon, , Portugal
Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano
Matosinhos Municipality, , Portugal
Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio
Porto, , Portugal
Hospital Cuf porto
Porto, , Portugal
Institutul Oncologic, Prof Dr Alexandru Trestioreanu
Bucharest, , Romania
Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca
Cluj-Napoca, , Romania
SC Medisprof SRL
Cluj-Napoca, , Romania
Centrul de Radioterapie Amethyst Cluj
Cluj-Napoca, , Romania
Centrul de Oncologie Sf Nectarie SRL
Craiova, , Romania
Institutul Regional de Oncologie Iasi
Iași, , Romania
Spitalul Municipal Ploiesti
Ploieşti, , Romania
SC Oncomed SRL
Timișoara, , Romania
National Cancer Center
Goyang-si Gyeonggi-do, , South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital Yonsei University Health System
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
The Catholic University of Korea Seoul St Marys Hospital
Seoul, , South Korea
Hospital Universitari Germans Trias i Pujol
Badalona, Catalonia, Spain
Hospital General Universitario de Valencia
Valencia, Valencia, Spain
Hospital General Universitario Gregorio Marañon
Madrid, , Spain
Clinica Universidad de Navarra
Madrid, , Spain
Fundacion Jimenez Diaz
Madrid, , Spain
Hospital Universitario Madrid Sanchinarro
Madrid, , Spain
Universitaetsspital Basel
Basel, , Switzerland
Hopitaux Universitaires de Geneve
Geneva, , Switzerland
Universitaetsspital Zuerich
Zurich, , Switzerland
Countries
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References
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Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30.
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Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023 Jun 20;41(18):3311-3317. doi: 10.1200/JCO.22.02524. Epub 2023 Apr 25.
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Related Links
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AmgenTrials clinical trials website
Other Identifiers
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20170543
Identifier Type: -
Identifier Source: org_study_id
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