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)

• ClinicalTrials.gov Identifier: NCT03600883
• Recruitment Status: Active, not recruiting
• First Posted: July 26, 2018
• Last Update Posted: February 26, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors.

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.

Condition or disease	Intervention/treatment	Phase
KRAS p.G12C Mutant Advanced Solid Tumors	Drug: sotorasib; Drug: Anti PD-1/L1; Drug: Midazolam	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 713 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and Sotorasib (AMG 510) Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)
• Actual Study Start Date: August 27, 2018
• Estimated Primary Completion Date: November 8, 2027
• Estimated Study Completion Date: November 8, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental: 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	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental: 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)	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation; Drug: Anti PD-1/L1; Administered as an intravenous (IV) infusion
Experimental: 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.	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation; Drug: Midazolam; Administered as an oral hydrochloride (HCI) syrup
Experimental: Phase 2 monotherapy dose comparison; Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental: Phase 1 Does escalation and Expansion monotherapy BID; BID 2L+solid tumors (fed state)	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation

Outcome Measures

Primary Outcome Measures :

1. Primary: Number of subjects with treatment-emergent adverse events [ Time Frame: 24 Months ]

   Treatment-emergent adverse events will be a primary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
   • Phase 2 monotherapy dose comparison
2. Primary: Number of subjects with treatment-related adverse events [ Time Frame: 24 Months ]

   Treatment-related adverse events will be a primary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
3. Primary: Number of subjects with grade ≥3 treatment-emergent adverse events [ Time Frame: 24 Months ]

   Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group:

   - Phase 2 monotherapy dose comparison

4. Primary: Number of subjects with serious adverse events [ Time Frame: 24 Months ]

   Serious adverse events will be a primary outcome measure in the following group:

   - Phase 2 monotherapy dose comparison

5. Primary: Number of subjects with adverse events of interest [ Time Frame: 24 Months ]

   Adverse events of interest will be a primary outcome measure in the following group:

   - Phase 2 monotherapy dose comparison

6. Primary: Number of subjects with clinically significant changes in vital signs [ Time Frame: Baseline to 24 Months ]

   Vital signs will be a primary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
7. Primary: Number of subjects with clinically significant changes in physical examination results [ Time Frame: Baseline to 24 Months ]

   Physical examinations will be a primary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
8. Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs) [ Time Frame: Baseline to 24 Months ]

   ECGs will be a primary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
9. Primary: Number of subjects with clinically significant changes in clinical laboratory values [ Time Frame: Baseline to 24 Months ]

   Abnormal clinical laboratory values will be a primary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
10. Primary: Number of subjects with dose-limiting toxicities (DLTs) [ Time Frame: 21 Days ]

    DLTs will be a primary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
    • Phase 1 combination arm with sotorasib and anti PD-1/L1
    • Phase 1 monotherapy treatment naïve advanced NSCLC
11. Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    ORR will be a primary outcome measure in the following group:

    • Phase 1 monotherapy treatment naïve advanced NSCLC
    • Phase 2 monotherapy
    • Phase 2 monotherapy dose comparison
12. Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    DOR will be a primary outcome measure in the following group:

    - Phase 1 monotherapy treatment naïve advanced NSCLC

13. Primary: Disease control as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    Disease control will be a primary outcome measure in the following group:

    - Phase 1 monotherapy treatment naïve advanced NSCLC

14. Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    Duration of SD will be a primary outcome measure in the following group:

    - Phase 1 monotherapy treatment naïve advanced NSCLC

15. Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    TTR will be a primary outcome measure in the following group:

    - Phase 1 monotherapy treatment naïve advanced NSCLC

Secondary Outcome Measures :

1. Secondary: Plasma concentration (Cmax) of sotorasib [ Time Frame: 15 Weeks ]

   Cmax will be a secondary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
   • Phase 2 monotherapy dose comparison
2. Secondary: Plasma concentration (Cmax) of midazolam [ Time Frame: 16 Days ]

   Cmax of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:

   - Phase 1 monotherapy treatment naïve advanced NSCLC

3. Secondary: Time to achieve Cmax (Tmax) of sotorasib [ Time Frame: 15 Weeks ]

   Tmax will be a secondary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
4. Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib [ Time Frame: 15 Weeks ]

   AUC will be a secondary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 1 monotherapy treatment naïve advanced NSCLC
   • Phase 2 monotherapy dose comparison
5. Secondary: Area under the plasma concentration-time curve (AUC) of midazolam [ Time Frame: 16 Days ]

   AUC of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:

   - Phase 1 monotherapy treatment naïve advanced NSCLC

6. Secondary: Clearance of midazolam from the plasma [ Time Frame: 16 Days ]

   Clearance of midazolam from the plasma will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:

   - Phase 1 monotherapy treatment naïve advanced NSCLC

7. Secondary: Terminal half-life (t1/2) of midazolam [ Time Frame: 16 Days ]

   t1/2 of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:

   - Phase 1 monotherapy treatment naïve advanced NSCLC

8. Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

   ORR will be a secondary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
9. Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

   DOR will be a secondary outcome measure for the following groups:

   • Phase 1 Dose Exploration Part 1 monotherapy
   • Phase 1 Dose Expansion Part 2 monotherapy
   • Phase 2 monotherapy
   • Phase 1 combination arm with sotorasib and anti PD-1/L1
   • Phase 2 monotherapy dose comparison
10. Secondary: Disease control as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    DOR will be a secondary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
    • Phase 2 monotherapy
    • Phase 1 combination arm with sotorasib and anti PD-1/L1
    • Phase 2 monotherapy dose comparison
11. Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    PFS will be a secondary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
    • Phase 2 monotherapy
    • Phase 1 combination arm with sotorasib and anti PD-1/L1
    • Phase 2 monotherapy dose comparison
    • Phase 1 monotherapy treatment naïve advanced NSCLC
12. Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    Duration of SD will be a secondary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
    • Phase 1 combination arm with sotorasib and anti PD-1/L1
13. Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria [ Time Frame: Baseline to 24 Months ]

    Depth of response will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

14. Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]

    DOR will be a secondary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
    • Phase 2 monotherapy
    • Phase 1 combination arm with sotorasib and anti PD-1/L1
    • Phase 2 monotherapy dose comparison
15. Secondary: Overall survival (OS) [ Time Frame: 24 Months ]

    OS will be a secondary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
    • Phase 2 monotherapy
    • Phase 1 combination arm with sotorasib and anti PD-1/L1
    • Phase 2 monotherapy dose comparison
    • Phase 1 monotherapy treatment naïve advanced NSCLC
16. Secondary: sotorasib exposure and QTc interval relationship [ Time Frame: 24 Months ]

    sotorasib exposure and QTc interval relationship will be a secondary outcome measure for the following groups:

    • Phase 1 Dose Exploration Part 1 monotherapy
    • Phase 1 Dose Expansion Part 2 monotherapy
17. Secondary: Progression-free survival (PFS) at 6 months [ Time Frame: 6 Months ]

    PFS at 6 months will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy

18. Secondary: Progression-free survival (PFS) at 12 months [ Time Frame: 12 Months ]

    PFS at 12 months will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy

19. Secondary: Overall survival (OS) at 12 months [ Time Frame: 12 Months ]

    OS at 12 months will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy

20. Secondary: Number of subjects with treatment-emergent adverse events [ Time Frame: 24 Months ]

    Treatment-emergent adverse events will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy

21. Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events [ Time Frame: 24 Months ]

    Grade ≥3 treatment-emergent adverse events will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy

22. Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30 [ Time Frame: 24 Months ]

    Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

23. Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13) [ Time Frame: 24 Months ]

    Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

24. Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC [ Time Frame: 24 Months ]

    Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

25. Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS) [ Time Frame: 24 Months ]

    Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

26. Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC [ Time Frame: 24 Months ]

    Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

27. Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30 [ Time Frame: 24 Months ]

    Treament related symptoms and impact on the subject will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

28. Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library) [ Time Frame: 24 Months ]

    Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

29. Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: 24 Months ]

    Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

30. Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30 [ Time Frame: Baseline to 24 Months ]

    Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:

    - Phase 2 monotherapy dose comparison

Eligibility Criteria

• 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

• Active brain metastases 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

Locations

United States, California

City of Hope National Medical Center

Duarte, California, United States, 91010

University of California Los Angeles

Los Angeles, California, United States, 90095

University of California at SF

San Francisco, California, United States, 94115

Sarcoma Oncology Research Center LLC

Santa Monica, California, United States, 90403

United States, Colorado

Rocky Mountain Cancer Centers

Denver, Colorado, United States, 80218

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States, 80218

United States, Connecticut

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States, 06510

United States, Delaware

Medical Oncology Hematology Consultants Helen F Graham Cancer Center

Newark, Delaware, United States, 19713

United States, Florida

University of Florida Health

Gainesville, Florida, United States, 32610

AdventHealth Orlando Infusion Center

Orlando, Florida, United States, 32804

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Winship Cancer Institute

Atlanta, Georgia, United States, 30322

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Maryland

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110-1093

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Laura and Isaac Perlmutter Cancer Center at New York University Langone

New York, New York, United States, 10016

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center, Morris Cancer Clinic

Durham, North Carolina, United States, 27710

United States, Ohio

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

University of Pittsburgh Medical Center Cancer Pavillion

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

Gibbs Cancer Center and Research Institute - Spartanburg

Spartanburg, South Carolina, United States, 29303

United States, Tennessee

Vanderbilt University Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Oncology - Austin Central

Austin, Texas, United States, 78731

Texas Oncology - Baylor

Dallas, Texas, United States, 75246

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Virginia

US Oncology Research Investigational Products Center

Fairfax, Virginia, United States, 22031

Virginia Cancer Specialists PC

Fairfax, Virginia, United States, 22031

Blue Ridge Cancer Care

Salem, Virginia, United States, 24153

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

Australia, New South Wales

Scientia Clinical Research Ltd

Randwick, New South Wales, Australia, 2031

Australia, Queensland

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia, 4102

Australia, South Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia, 5011

Australia, Victoria

Peter MacCallum Cancer Centre

Parkville, Victoria, Australia, 3050

Austria

Medizinische Universitaet Graz

Graz, Austria, 8036

Medizinische Universitaet Innsbruck

Innsbruck, Austria, 6020

Universitaetsklinikum Krems

Krems, Austria, 3500

Universitaetsklinikum Allgemeines Krankenhaus Wien

Wien, Austria, 1090

Krankenhaus Nord - Klinik Floridsdorf

Wien, Austria, 1210

Belgium

Institut Jules Bordet

Brussels, Belgium, B-1070

Grand Hopital de Charleroi

Charleroi, Belgium, 6000

Universitair Ziekenhuis Antwerpen

Edegem, Belgium, 2650

Ziekenhuis Oost-Limburg

Genk, Belgium, 3600

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, Belgium, 3500

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Belgium, 3000

Centre Hospitalier Universitaire de Liege

Liege, Belgium, 4000

AZ Delta Campus Rumbeke

Roeselare, Belgium, 8800

Brazil

Irmandade da Santa Casa de Misericordia de Porto Alegre, Nucleo de Novos Tratamentos em Cancer

Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170

Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul

Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

Sao Paulo, São Paulo, Brazil, 01308-050

Oncologia Rede D´Or

Sao Paulo, São Paulo, Brazil, 04501-000

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil, 15090-000

Instituto Coi

Rio de Janeiro, Brazil, 20231-050

Canada, Alberta

Tom Baker Cancer Centre

Calgary, Alberta, Canada, T2N 4N2

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

London Regional Cancer Program, London Health Sciences Centre

London, Ontario, Canada, N6A 5W9

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada, K1H 8L6

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

McGill University Health Centre Glen Site

Montreal, Quebec, Canada, H4A 3J1

France

Institut Bergonie

Bordeaux, France, 33076

Centre Hospitalier Intercommunal de Créteil

Créteil, France, 94010

Hopital de la Timone

Marseille cedex 5, France, 13385

Institut Curie

Paris, France, 75005

Institut Claudius Regaud

Toulouse cedex 9, France, 31059

Gustave Roussy

Villejuif, France, 94805

Germany

Universitätsklinikum Essen

Essen, Germany, 45147

Universitatsklinikum Koln

Köln, Germany, 50937

Klinikum der Universität München Campus Grosshadern

München, Germany, 81377

Greece

Henry Dunant Hospital Center

Athens, Greece, 11526

Metropolitan Hospital

Athens, Greece, 18547

University Hospital of Heraklion

Heraklion - Crete, Greece, 71500

Theagenion Cancer Hospital

Thessaloniki, Greece, 54007

Agios Loukas Clinic

Thessaloniki, Greece, 55236

Hungary

Semmelweis Egyetem

Budapest, Hungary, 1083

Orszagos Koranyi Pulmonologiai Intezet

Budapest, Hungary, 1121

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvar, Hungary, 7400

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Szekesfehervar, Hungary, 8000

Szent Borbala Korhaz

Tatabanya, Hungary, 2800

Tudogyogyintezet Torokbalint

Torokbalint, Hungary, 2045

Japan

Aichi Cancer Center

Nagoya-shi, Aichi, Japan, 464-8681

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan, 277-8577

National Hospital Organization Shikoku Cancer Center

Matsuyama-shi, Ehime, Japan, 791-0280

National Hospital Organization Kyushu Cancer Center

Fukuoka-shi, Fukuoka, Japan, 811-1395

National Hospital Organization Hokkaido Cancer Center

Sapporo-shi, Hokkaido, Japan, 003-0804

St Marianna University Hospital

Kawasaki-shi, Kanagawa, Japan, 216-8511

Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center

Yokohama-shi, Kanagawa, Japan, 241-8515

Sendai Kousei Hospital

Sendai-shi, Miyagi, Japan, 980-0873

Niigata Cancer Center Hospital

Niigata-shi, Niigata, Japan, 951-8566

Okayama University Hospital

Okayama-shi, Okayama, Japan, 700-8558

Kansai Medical University Hospital

Hirakata-shi, Osaka, Japan, 573-1191

Osaka International Cancer Institute

Osaka-shi, Osaka, Japan, 541-8567

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan, 411-8777

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, Japan, 135-8550

Wakayama Medical University Hospital

Wakayama-shi, Wakayama, Japan, 641-8510

Korea, Republic of

National Cancer Center

Goyang-si Gyeonggi-do, Korea, Republic of, 10408

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Severance Hospital Yonsei University Health System

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 06351

The Catholic University of Korea Seoul St Marys Hospital

Seoul, Korea, Republic of, 06591

Portugal

Fundacao Champalimaud

Lisboa, Portugal, 1400-038

Centro Hospitalar Universitario de Lisboa Norte EPE - Hospital Pulido Valente

Lisboa, Portugal, 1769-001

Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano

Matosinhos, Portugal, 4464-513

Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio

Porto, Portugal, 4099-001

Hospital Cuf porto

Porto, Portugal, 4100-180

Romania

Institutul Oncologic, Prof Dr Alexandru Trestioreanu

Bucuresti, Romania, 022328

Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca

Cluj Napoca, Romania, 400015

SC Medisprof SRL

Cluj Napoca, Romania, 400641

Centrul de Radioterapie Amethyst Cluj

Cluj Napoca, Romania, 407280

Centrul de Oncologie Sf Nectarie SRL

Craiova, Romania, 200347

Institutul Regional de Oncologie Iasi

Iasi, Romania, 700483

Spitalul Municipal Ploiesti

Ploiesti, Romania, 100337

SC Oncomed SRL

Timisoara, Romania, 300239

Spain

Hospital Universitari Germans Trias i Pujol

Badalona, Cataluña, Spain, 08916

Hospital General Universitario de Valencia

Valencia, Comunidad Valenciana, Spain, 46014

Hospital General Universitario Gregorio Marañon

Madrid, Spain, 28009

Clinica Universidad de Navarra

Madrid, Spain, 28027

Fundacion Jimenez Diaz

Madrid, Spain, 28040

Hospital Universitario Madrid Sanchinarro

Madrid, Spain, 28050

Switzerland

Universitaetsspital Basel

Basel, Switzerland, 4031

Hopitaux Universitaires de Geneve

Geneve, Switzerland, 1211

Universitaetsspital Zuerich

Zurich, Switzerland, 8091

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

Publications:

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.

Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24;384(25):2371-2381. doi: 10.1056/NEJMoa2103695. Epub 2021 Jun 4.

Fakih MG, Kopetz S, Kuboki Y, Kim TW, Munster PN, Krauss JC, Falchook GS, Han SW, Heinemann V, Muro K, Strickler JH, Hong DS, Denlinger CS, Girotto G, Lee MA, Henary H, Tran Q, Park JK, Ngarmchamnanrith G, Prenen H, Price TJ. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15.

Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20.

Zhao Y, Murciano-Goroff YR, Xue JY, Ang A, Lucas J, Mai TT, Da Cruz Paula AF, Saiki AY, Mohn D, Achanta P, Sisk AE, Arora KS, Roy RS, Kim D, Li C, Lim LP, Li M, Bahr A, Loomis BR, de Stanchina E, Reis-Filho JS, Weigelt B, Berger M, Riely G, Arbour KC, Lipford JR, Li BT, Lito P. Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature. 2021 Nov;599(7886):679-683. doi: 10.1038/s41586-021-04065-2. Epub 2021 Nov 10.

Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21.

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.

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 benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary. Future Oncol. 2024 Jan;20(3):113-120. doi: 10.2217/fon-2023-0560. Epub 2023 Nov 27.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lanman BA, Allen JR, Allen JG, Amegadzie AK, Ashton KS, Booker SK, Chen JJ, Chen N, Frohn MJ, Goodman G, Kopecky DJ, Liu L, Lopez P, Low JD, Ma V, Minatti AE, Nguyen TT, Nishimura N, Pickrell AJ, Reed AB, Shin Y, Siegmund AC, Tamayo NA, Tegley CM, Walton MC, Wang HL, Wurz RP, Xue M, Yang KC, Achanta P, Bartberger MD, Canon J, Hollis LS, McCarter JD, Mohr C, Rex K, Saiki AY, San Miguel T, Volak LP, Wang KH, Whittington DA, Zech SG, Lipford JR, Cee VJ. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT03600883
• Other Study ID Numbers: 20170543
• First Posted: July 26, 2018
• Last Update Posted: February 26, 2024
• Last Verified: February 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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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: https://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Sotorasib; Midazolam; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Antineoplastic Agents