Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

NCT05198934 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: 201901722024-511187-81-00
• Study Type: interventional
• Target: 160
• Locations: 12 countries
• Sites: 105

Brief Summary

The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg QD and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib).

Conditions

Colorectal Cancer (CRC)

Keywords

Sotorasib; AMG 510; Panitumumab; Metastatic colorectal cancer; Kirsten rat sarcoma p.G12C mutation

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Approximately 3 years

Secondary Outcomes (22)

• Overall Survival (OS)

  Approximately 3 years

• Objective Response Rate (ORR)

  Approximately 3 years

• Duration of Response (DOR)

  Approximately 3 years

• Time to Response (TTR)

  Approximately 3 years

• Disease Control Rate (DCR)

  Approximately 3 years

Study Arms (3)

Arm A: Sotorasib 960 mg QD + panitumumab

EXPERIMENTAL

Drug: Sotorasib; Drug: Panitumumab

Arm B: Sotorasib 240 mg QD + panitumumab

EXPERIMENTAL

Drug: Sotorasib; Drug: Panitumumab

Arm C : Investigator's choice

ACTIVE COMPARATOR

Participants will be administered trifluridine and tipiracil, or regorafenib

Drug: Trifluridine and Tipiracil; Drug: Regorafenib

Interventions

Panitumumab DRUG

Panitumumab will be administered as intravenous (IV) infusion

Also known as: Vectibix

Arm A: Sotorasib 960 mg QD + panitumumab; Arm B: Sotorasib 240 mg QD + panitumumab

Trifluridine and Tipiracil DRUG

Trifluridine and Tipiracil will be administered orally

Also known as: Lonsurf

Arm C : Investigator's choice

Sotorasib DRUG

Sotorasib will be administered orally

Also known as: AMG 510, Lumakras, Lumykras

Arm A: Sotorasib 960 mg QD + panitumumab; Arm B: Sotorasib 240 mg QD + panitumumab

Regorafenib DRUG

Regorafenib will be administered orally

Also known as: Stivarga

Arm C : Investigator's choice

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
• Age ≥18 years.
• Pathologically documented metastatic colorectal adenocarcinoma with Kirsten rat sarcoma (KRAS) p.G12C mutation as determined by prospective central testing, using the analytically validated Qiagen Therascreen KRAS RGQ polymerase chain reaction Kit in CRC as an investigational device demonstrating a KRAS p.G12C mutation is present. Local testing and documentation of KRAS p.G12C mutation should have been previously performed as part of standard of care.
• Participants will have received at least 1 prior line of therapy for metastatic disease. Participants must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless the participant, in the opinion of the investigator, is not a candidate for fluoropyrimidine, irinotecan, or oxaliplatin, in which case, the participant may be eligible after investigator discussion with Amgen medical monitor provided participant has received at least one prior line of therapy for metastatic disease and provided trifluridine and tipiracil or regorafenib is deemed the appropriate next line of therapy for the participant.
• Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.
• Life expectancy of \>3 months, in the opinion of the investigator.
• Adequate hematologic and end-organ function, defined as the following within 2 weeks prior to cycle 1 day 1:
• Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility).
• Hemoglobin ≥9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility).
• Platelet count ≥100 x 10\^9/L (without transfusion within 2 weeks of laboratory test used to determine eligibility).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal (ULN).
• Serum bilirubin ≤1.0 x ULN. For participants with Gilbert's disease, total bilirubin or direct bilirubin needs to be ≤1.0 x ULN.
• International normalized ratio (INR) and activated partial thromboplastin time (or partial thromboplastin time) ≤1.5 x ULN. Prothrombin time (PT) ≤1.5 x ULN may be used instead of INR for sites whose labs do not report INR.
• Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥30 mL/min/1.73 m\^2.

You may not qualify if:

• Active brain metastases. Participants who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade ≤2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up magnetic resonance imaging (MRI) performed within 28 days of day 1 shows no progression or new lesions appearing.
• History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥2 years.
• History of other malignancy within the past 3 years, with the following exceptions:
• Malignancy treated with curative intent and with no known active disease present for ≥3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ.
• Leptomeningeal disease.
• Significant gastrointestinal (GI) disorder that results in significant malabsorption, requirement for intravenous (IV) alimentation, or inability to take oral medication.
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to randomization, unstable arrhythmias or unstable angina.
• Previous treatment with a KRAS G12C inhibitor.

Sponsors & Collaborators

• Amgen: lead

Study Sites (105)

Central Alabama Research

Birmingham, Alabama, 35209, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Johns Hopkins University School of Medicine

Washington D.C., District of Columbia, 20016, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Lakes Research LLC

Miami Lakes, Florida, 33014, United States

Location

Northwest Georgia Oncology Centers PC

Marietta, Georgia, 30060, United States

Location

University of Michigan

Ann Arbor, Michigan, 48106-0995, United States

Location

Revive Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Sparrow Clinical Research Institute

Lansing, Michigan, 48912, United States

Location

Revive Research Institute

Sterling Heights, Michigan, 48314, United States

Location

Upstate University Hospital

Syracuse, New York, 13210, United States

Location

White Plains Hospital Center for Cancer Care

White Plains, New York, 10601, United States

Location

Moses H Cone Memorial Hospital

Greensboro, North Carolina, 27403, United States

Location

The Mark H Zangmeister Center

Columbus, Ohio, 43210, United States

Location

Lancaster General Hospital Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania, 17601, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Kelsey Research Foundation

Houston, Texas, 77025, United States

Location

Best Cancer Care & Hematology

Houston, Texas, 77089, United States

Location

Lumi Research

Kingwood, Texas, 77339, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

GenesisCare -North Shore (Oncology)

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot

Lyon Cédex 3, 69437, France

Location

Institut regional du Cancer Montpellier

Montpellier, 34298, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Hôpital Haut -lévêque

Pessac, 33604, France

Location

Charite Universitaetsmedizin Berlin, Charité Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, 01307, Germany

Location

Universitaetsmedizin Goettingen - Georg-August-Universitaet

Göttingen, 37075, Germany

Location

Klinikum der Universitaet Muenchen Campus Grosshadern

München, 81377, Germany

Location

Universitaetsklinikum der Eberhard Karls Universitaet Tuebingen

Tübingen, 72076, Germany

Location

General Hospital of Athens Laiko

Athens, 11527, Greece

Location

Evgenidio Hospital I Agia Trias

Athens, 11528, Greece

Location

Hygeia Hospital

Athens, 15123, Greece

Location

University Hospital of Heraklion

Heraklion - Crete, 71500, Greece

Location

University Hospital of Patras

Pátrai, 26504, Greece

Location

Theagenion Anticancer Hospital

Thessaloniki, 54007, Greece

Location

Agios Loukas Clinic

Thessaloniki, 55236, Greece

Location

Istituto Ospedaliero Fondazione Poliambulanza

Brescia, 25124, Italy

Location

Azienda Ospedaliera Rilievo Nazionale e Alta Specializzazione Garibaldi Nesima

Catania, 95122, Italy

Location

Azienda Ospedaliera Santa Croce e Carle

Confreria (CN), 12100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Ospedale Policlinico San Martino IRCCS

Genova, 16132, Italy

Location

Azienda Sanitaria Locale 5 Spezzino Ospedale S Andrea

La Spezia, 19100, Italy

Location

Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II

Lecce, 73100, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria di Cagliari Policlinico Duilio Casula

Monserrato CA, 09042, Italy

Location

Azienda Ospedaliero Universitaria Luigi Vanvitelli

Naples, 80131, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale

Naples, 80131, Italy

Location

Azienda Ospedaliero Universitaria Maggiore della Carita

Novara, 28100, Italy

Location

Istituto Oncologico Veneto IRCCS

Padova, 35128, Italy

Location

Azienda Ospedaliera Universitaria Pisana Ospedale Santa Chiara

Pisa, 56126, Italy

Location

Azienda Ospedaliera San Carlo

Potenza, 85100, Italy

Location

Azienda Unita Sanitaria Locale di Reggio Emilia Arcispedale Santa Maria Nuova

Reggio Emilia, 42100, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera San Giovanni Addolorata

Roma, 00184, Italy

Location

Fondazione Policlinico Tor Vergata

Roma (RM), 00133, Italy

Location

Azienda Ospedaliera Cardinale Giovanni Panico

Tricase, 73039, Italy

Location

Azienda Unita Locale Socio Sanitaria Berica 8

Vicenza, 36100, Italy

Location

Aichi Medical University Hospital

Nagakute-shi, Aichi-ken, 480-1195, Japan

Location

Chiba Cancer Center

Chiba, Chiba, 260-8717, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, 811-1395, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo Cancer Center

Akashi-shi, Hyōgo, 673-8558, Japan

Location

St Marianna University Hospital

Kawasaki-shi, Kanagawa, 216-8511, Japan

Location

Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, Osaka, 540-0006, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Saitama Cancer Center

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Health Pharma Professional Research SA de CV

Mexico City, Mexico City, 03100, Mexico

Location

Superare Centro de Infusion SA de CV

Mexico City, Mexico City, 06760, Mexico

Location

Trials In Medicine SC

Mexico City, 06700, Mexico

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Reina Sofia

Córdoba, Andalusia, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Andalusia, 18014, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

Location

Complexo Hospitalario Universitario de Ourense

Ourense, Galicia, 32005, Spain

Location

Hospital Universitario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital General Universitario de Elche

Elche, Valencia, 03203, Spain

Location

Hospital General Universitario de Valencia

Valencia, Valencia, 46014, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Maidstone Hospital

Maidstone, ME16 9QQ, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, HA6 2RN, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (3)

• Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. doi: 10.1056/NEJMoa2308795. Epub 2023 Oct 22.

  PMID: 37870968 BACKGROUND

• Pietrantonio F, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Tran Q, Cremolini C, Fakih M. Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer. J Clin Oncol. 2025 Jul;43(19):2147-2154. doi: 10.1200/JCO-24-02026. Epub 2025 Apr 11.

  PMID: 40215429 BACKGROUND

• Modest DP, Fakih M, Salvatore L, Esaki T, Lopez-Bravo DP, Taieb J, Karamouzis M, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Cremolini C, Tran Q, Chan E, Chao J, Majer IM, Pietrantonio F. Health-related quality of life in patients with KRASG12C-mutated chemorefractory metastatic colorectal cancer treated with sotorasib plus panitumumab or standard of care (CodeBreaK 300): results from a phase 3, randomised clinical trial. Lancet Oncol. 2025 Sep;26(9):1240-1251. doi: 10.1016/S1470-2045(25)00352-3. Epub 2025 Aug 11.

  PMID: 40812325 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sotorasib; Panitumumab; trifluridine tipiracil drug combination; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: January 20, 2022
• Study Start: April 19, 2022
• Primary Completion: July 16, 2025
• Study Completion: April 14, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

FR (4); DE (5); GR (7); IT (22); GB (6); US (20); TW (5); AU (4); JP (15); ES (10); KR (4); ME (3)