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

NCT ID: NCT05198934

Last Updated: 2026-02-06

Study Results

Results pending

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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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-19

Study Completion Date

2026-05-14

Brief Summary

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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).

Detailed Description

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Conditions

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Colorectal Cancer (CRC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Sotorasib 960 mg QD + panitumumab

Group Type EXPERIMENTAL

Sotorasib

Intervention Type DRUG

Sotorasib will be administered orally

Panitumumab

Intervention Type DRUG

Panitumumab will be administered as intravenous (IV) infusion

Arm B: Sotorasib 240 mg QD + panitumumab

Group Type EXPERIMENTAL

Sotorasib

Intervention Type DRUG

Sotorasib will be administered orally

Panitumumab

Intervention Type DRUG

Panitumumab will be administered as intravenous (IV) infusion

Arm C : Investigator's choice

Participants will be administered trifluridine and tipiracil, or regorafenib

Group Type ACTIVE_COMPARATOR

Trifluridine and Tipiracil

Intervention Type DRUG

Trifluridine and Tipiracil will be administered orally

Regorafenib

Intervention Type DRUG

Regorafenib will be administered orally

Interventions

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Sotorasib

Sotorasib will be administered orally

Intervention Type DRUG

Panitumumab

Panitumumab will be administered as intravenous (IV) infusion

Intervention Type DRUG

Trifluridine and Tipiracil

Trifluridine and Tipiracil will be administered orally

Intervention Type DRUG

Regorafenib

Regorafenib will be administered orally

Intervention Type DRUG

Other Intervention Names

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AMG 510, Lumakras, Lumykras Vectibix Lonsurf Stivarga

Eligibility Criteria

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Inclusion Criteria

* 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.
* Fridericia's Correction Formula (QTcF) ≤470 msec.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Central Alabama Research

Birmingham, Alabama, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California Irvine

Orange, California, United States

Site Status

Johns Hopkins University School of Medicine

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

Site Status

Cancer Specialists of North Florida

Jacksonville, Florida, United States

Site Status

Lakes Research LLC

Miami Lakes, Florida, United States

Site Status

Northwest Georgia Oncology Centers PC

Marietta, Georgia, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Revive Research Institute

Farmington Hills, Michigan, United States

Site Status

Sparrow Clinical Research Institute

Lansing, Michigan, United States

Site Status

Revive Research Institute

Sterling Heights, Michigan, United States

Site Status

Upstate University Hospital

Syracuse, New York, United States

Site Status

White Plains Hospital Center for Cancer Care

White Plains, New York, United States

Site Status

Moses H Cone Memorial Hospital

Greensboro, North Carolina, United States

Site Status

The Mark H Zangmeister Center

Columbus, Ohio, United States

Site Status

Lancaster General Hospital Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Kelsey Research Foundation

Houston, Texas, United States

Site Status

Best Cancer Care & Hematology

Houston, Texas, United States

Site Status

Lumi Research

Kingwood, Texas, United States

Site Status

Chris OBrien Lifehouse

Camperdown, New South Wales, Australia

Site Status

GenesisCare -North Shore (Oncology)

St Leonards, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot

Lyon Cédex 3, , France

Site Status

Institut regional du Cancer Montpellier

Montpellier, , France

Site Status

Hôpital Européen Georges Pompidou

Paris, , France

Site Status

Hôpital Haut -lévêque

Pessac, , France

Site Status

Charite Universitaetsmedizin Berlin, Charité Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, , Germany

Site Status

Universitaetsmedizin Goettingen - Georg-August-Universitaet

Göttingen, , Germany

Site Status

Klinikum der Universitaet Muenchen Campus Grosshadern

München, , Germany

Site Status

Universitaetsklinikum der Eberhard Karls Universitaet Tuebingen

Tübingen, , Germany

Site Status

General Hospital of Athens Laiko

Athens, , Greece

Site Status

Evgenidio Hospital I Agia Trias

Athens, , Greece

Site Status

Hygeia Hospital

Athens, , Greece

Site Status

University Hospital of Heraklion

Heraklion - Crete, , Greece

Site Status

University Hospital of Patras

Pátrai, , Greece

Site Status

Theagenion Anticancer Hospital

Thessaloniki, , Greece

Site Status

Agios Loukas Clinic

Thessaloniki, , Greece

Site Status

Istituto Ospedaliero Fondazione Poliambulanza

Brescia, , Italy

Site Status

Azienda Ospedaliera Rilievo Nazionale e Alta Specializzazione Garibaldi Nesima

Catania, , Italy

Site Status

Azienda Ospedaliera Santa Croce e Carle

Confreria (CN), , Italy

Site Status

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Site Status

Ospedale Policlinico San Martino IRCCS

Genova, , Italy

Site Status

Azienda Sanitaria Locale 5 Spezzino Ospedale S Andrea

La Spezia, , Italy

Site Status

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

Lecce, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Azienda Ospedaliero Universitaria di Cagliari Policlinico Duilio Casula

Monserrato CA, , Italy

Site Status

Azienda Ospedaliero Universitaria Luigi Vanvitelli

Napoli, , Italy

Site Status

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

Napoli, , Italy

Site Status

Azienda Ospedaliero Universitaria Maggiore della Carita

Novara, , Italy

Site Status

Istituto Oncologico Veneto IRCCS

Padua, , Italy

Site Status

Azienda Ospedaliera Universitaria Pisana Ospedale Santa Chiara

Pisa, , Italy

Site Status

Azienda Ospedaliera San Carlo

Potenza, , Italy

Site Status

Azienda Unita Sanitaria Locale di Reggio Emilia Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status

Azienda Ospedaliera San Giovanni Addolorata

Roma, , Italy

Site Status

Fondazione Policlinico Tor Vergata

Roma (RM), , Italy

Site Status

Azienda Ospedaliera Cardinale Giovanni Panico

Tricase, , Italy

Site Status

Azienda Unita Locale Socio Sanitaria Berica 8

Vicenza, , Italy

Site Status

Aichi Medical University Hospital

Nagakute-shi, Aichi-ken, Japan

Site Status

Chiba Cancer Center

Chiba, Chiba, Japan

Site Status

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Site Status

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

Site Status

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, Japan

Site Status

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status

Hyogo Cancer Center

Akashi-shi, Hyōgo, Japan

Site Status

St Marianna University Hospital

Kawasaki-shi, Kanagawa, Japan

Site Status

Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status

National Hospital Organization Osaka National Hospital

Osaka, Osaka, Japan

Site Status

Osaka University Hospital

Suita-shi, Osaka, Japan

Site Status

Saitama Cancer Center

Kitaadachi-gun, Saitama, Japan

Site Status

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan

Site Status

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, Japan

Site Status

Health Pharma Professional Research SA de CV

Mexico City, Mexico City, Mexico

Site Status

Superare Centro de Infusion SA de CV

Mexico City, Mexico City, Mexico

Site Status

Trials In Medicine SC

Mexico City, , Mexico

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Universitario Reina Sofia

Córdoba, Andalusia, Spain

Site Status

Hospital Universitario Virgen de las Nieves

Granada, Andalusia, Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Site Status

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, Spain

Site Status

Complexo Hospitalario Universitario de Ourense

Ourense, Galicia, Spain

Site Status

Hospital Universitario de Navarra

Pamplona, Navarre, Spain

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Hospital General Universitario de Elche

Elche, Valencia, Spain

Site Status

Hospital General Universitario de Valencia

Valencia, Valencia, Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, , Taiwan

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

Maidstone Hospital

Maidstone, , United Kingdom

Site Status

Mount Vernon Cancer Centre

Northwood, , United Kingdom

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States Australia France Germany Greece Italy Japan Mexico South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 37870968 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 40215429 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 40812325 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2024-511187-81-00

Identifier Type: CTIS

Identifier Source: secondary_id

20190172

Identifier Type: -

Identifier Source: org_study_id

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