Colorectal Cancer (CRC)Phase 3CodeBreak300NCT05198934
Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
A Phase 3 study testing Sotorasib, Panitumumab and Trifluridine and Tipiracil in people with Colorectal Cancer (CRC), run by Amgen at 105 sites in 12 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Colorectal Cancer (CRC)
- What is being tested?
- Sotorasib, Panitumumab and Trifluridine and Tipiracil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 105 sitesin 12 countries
- Study dates
- 19 Apr 2022to 14 Apr 2026
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
105 sites in 12 countries.
105 sites in 12 countries
Italy22 sites
Istituto Ospedaliero Fondazione Poliambulanza
Brescia, 25124
Azienda Ospedaliera Rilievo Nazionale e Alta Specializzazione Garibaldi Nesima
Catania, 95122
Azienda Ospedaliera Santa Croce e Carle
Confreria (CN), 12100
Azienda Ospedaliera Universitaria Careggi
Florence, 50134
Ospedale Policlinico San Martino IRCCS
Genova, 16132
Azienda Sanitaria Locale 5 Spezzino Ospedale S Andrea
La Spezia, 19100
Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
Lecce, 73100
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, 20162
Azienda Ospedaliero Universitaria di Cagliari Policlinico Duilio Casula
Monserrato CA, 09042
Azienda Ospedaliero Universitaria Luigi Vanvitelli
Naples, 80131
Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale
Naples, 80131
Azienda Ospedaliero Universitaria Maggiore della Carita
Novara, 28100
Istituto Oncologico Veneto IRCCS
Padova, 35128
Azienda Ospedaliera Universitaria Pisana Ospedale Santa Chiara
Pisa, 56126
Azienda Ospedaliera San Carlo
Potenza, 85100
Azienda Unita Sanitaria Locale di Reggio Emilia Arcispedale Santa Maria Nuova
Reggio Emilia, 42100
Policlinico Universitario Agostino Gemelli
Roma, 00168
Azienda Ospedaliera San Giovanni Addolorata
Roma, 00184
Fondazione Policlinico Tor Vergata
Roma (RM), 00133
Azienda Ospedaliera Cardinale Giovanni Panico
Tricase, 73039
Azienda Unita Locale Socio Sanitaria Berica 8
Vicenza, 36100
United States20 sites
University of Michigan
Ann Arbor, Michigan, 48106-0995
Central Alabama Research
Birmingham, Alabama, 35209
The Mark H Zangmeister Center
Columbus, Ohio, 43210
City of Hope National Medical Center
Duarte, California, 91010
Revive Research Institute
Farmington Hills, Michigan, 48334
Moses H Cone Memorial Hospital
Greensboro, North Carolina, 27403
Kelsey Research Foundation
Houston, Texas, 77025
Best Cancer Care & Hematology
Houston, Texas, 77089
Cancer Specialists of North Florida
Jacksonville, Florida, 32256
Lumi Research
Kingwood, Texas, 77339
Lancaster General Hospital Ann B Barshinger Cancer Institute
Lancaster, Pennsylvania, 17601
Sparrow Clinical Research Institute
Lansing, Michigan, 48912
Northwest Georgia Oncology Centers PC
Marietta, Georgia, 30060
Lakes Research LLC
Miami Lakes, Florida, 33014
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
University of California Irvine
Orange, California, 92868
Revive Research Institute
Sterling Heights, Michigan, 48314
Upstate University Hospital
Syracuse, New York, 13210
Johns Hopkins University School of Medicine
Washington D.C., District of Columbia, 20016
White Plains Hospital Center for Cancer Care
White Plains, New York, 10601
Japan15 sites
Hyogo Cancer Center
Akashi-shi, Hyōgo, 673-8558
Chiba Cancer Center
Chiba, Chiba, 260-8717
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
St Marianna University Hospital
Kawasaki-shi, Kanagawa, 216-8511
Saitama Cancer Center
Kitaadachi-gun, Saitama, 362-0806
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-ku, Tokyo, 135-8550
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
Aichi Medical University Hospital
Nagakute-shi, Aichi-ken, 480-1195
National Hospital Organization Osaka National Hospital
Osaka, Osaka, 540-0006
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Osaka University Hospital
Suita-shi, Osaka, 565-0871
Shizuoka Cancer Center
Sunto-gun, Shizuoka, 411-8777
Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
Spain10 sites
Hospital Universitari Vall d Hebron
Barcelona, Catalonia, 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, Catalonia, 08041
Hospital Universitario Reina Sofia
Córdoba, Andalusia, 14004
Hospital General Universitario de Elche
Elche, Valencia, 03203
Hospital Universitario Virgen de las Nieves
Granada, Andalusia, 18014
Hospital Universitario La Paz
Madrid, 28046
Complexo Hospitalario Universitario de Ourense
Ourense, Galicia, 32005
Hospital Universitario de Navarra
Pamplona, Navarre, 31008
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Hospital General Universitario de Valencia
Valencia, Valencia, 46014
Greece7 sites
General Hospital of Athens Laiko
Athens, 11527
Evgenidio Hospital I Agia Trias
Athens, 11528
Hygeia Hospital
Athens, 15123
University Hospital of Heraklion
Heraklion - Crete, 71500
University Hospital of Patras
Pátrai, 26504
Theagenion Anticancer Hospital
Thessaloniki, 54007
Agios Loukas Clinic
Thessaloniki, 55236
United Kingdom6 sites
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Royal Free Hospital
London, NW3 2QG
Royal Marsden Hospital
London, SW3 6JJ
Maidstone Hospital
Maidstone, ME16 9QQ
Mount Vernon Cancer Centre
Northwood, HA6 2RN
Royal Marsden Hospital
Sutton, SM2 5PT
Germany5 sites
Charite Universitaetsmedizin Berlin, Charité Campus Virchow-Klinikum
Berlin, 13353
Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
Dresden, 01307
Universitaetsmedizin Goettingen - Georg-August-Universitaet
Göttingen, 37075
Klinikum der Universitaet Muenchen Campus Grosshadern
München, 81377
Universitaetsklinikum der Eberhard Karls Universitaet Tuebingen
Tübingen, 72076
Taiwan5 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 80756
National Cheng Kung University Hospital
Tainan, 70403
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
Taoyuan, 33305
Australia4 sites
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050
GenesisCare -North Shore (Oncology)
St Leonards, New South Wales, 2065
Westmead Hospital
Westmead, New South Wales, 2145
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011
France4 sites
Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot
Lyon Cédex 3, 69437
Institut regional du Cancer Montpellier
Montpellier, 34298
Hôpital Européen Georges Pompidou
Paris, 75015
Hôpital Haut -lévêque
Pessac, 33604
South Korea4 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Mexico3 sites
Health Pharma Professional Research SA de CV
Mexico City, Mexico City, 03100
Superare Centro de Infusion SA de CV
Mexico City, Mexico City, 06760
Trials In Medicine SC
Mexico City, 06700
About this study
Official title: A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
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)
- Being tested
- Sotorasib, Panitumumab, Trifluridine and Tipiracil, Regorafenib
- Keywords
- Sotorasib, AMG 510, Panitumumab, Metastatic colorectal cancer, Kirsten rat sarcoma p.G12C mutation
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotorasibDrug
Also called AMG 510, Lumakras, Lumykras
Sotorasib will be administered orally
PanitumumabDrug
Also called Vectibix
Panitumumab will be administered as intravenous (IV) infusion
Trifluridine and TipiracilDrug
Also called Lonsurf
Trifluridine and Tipiracil will be administered orally
RegorafenibDrug
Also called Stivarga
Regorafenib will be administered orally
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Sotorasib 960 mg QD + panitumumab | Experimental | Not described Receives: Drug: Sotorasib; Drug: Panitumumab |
| Arm B: Sotorasib 240 mg QD + panitumumab | Experimental | Not described Receives: Drug: Sotorasib; Drug: Panitumumab |
| Arm C : Investigator's choice | Active comparator | Participants will be administered trifluridine and tipiracil, or regorafenib Receives: Drug: Trifluridine and Tipiracil; Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by BICR
PFS was defined as time from randomization until disease progression or death from any cause, whichever occurred first, for all participants. Progression was assessed using RECIST v1.1 per BICR.
Measured: From randomization until DCO or death; median (min, max) time on trial was 6.23 (0.1, 14.0) months
Secondary outcomes (22)
Overall Survival (OS)
OS was defined as time from randomization until death from any cause.
Measured: Approximately 3 years
Objective Response Rate (ORR) Per RECIST Version 1.1 as Assessed by BICR
Objective response was defined as best overall response (BOR) of complete response (CR) or partial response (PR), as defined by RECIST version 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. Responses were assessed based on BICR.
Measured: Approximately 3 years
Duration of Response (DOR) Per RECIST Version 1.1 as Assessed by BICR
DOR was defined as time from first evidence of PR or CR until progressive disease (PD) or death due to any cause, whichever occurs first. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Measured: Approximately 3 years
Time to Response (TTR) as Assessed by BICR
TTR was defined as time from randomization to the first evidence of PR or CR based on BICR. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
Measured: Approximately 3 years
Disease Control Rate (DCR) as Assessed by BICR
DCR was defined as the percentage of participants with the BOR of CR, PR or stable disease (SD) of at least 7 weeks based on BICR. CR was defined as disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on trial (this includes baseline sum if that is the smallest on trial).
Measured: Approximately 3 years
PFS Per RECIST Version 1.1 as Based on Investigator Assessment
PFS by investigator assessment was defined as the time from randomization until PD or death due to any cause, whichever occurs first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions.
Measured: Approximately 3 years
ORR Per RECIST Version 1.1 as Based on Investigator Assessment
ORR was defined as BOR of CR or PR, as defined by RECIST version 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. Responses were assessed based on investigator assessment.
Measured: Approximately 3 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were events with onset after the administration of the first dose of any trial treatment up to EOT or 30 days of the last dose of any trial treatment, or prior to first dose of crossed over treatment, whichever occurred earlier. Clinically significant changes in vital signs, and clinical laboratory tests were included as TEAEs.
Measured: Approximately 3 years
Change From Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory - Short Form (BFI-SF)
Item 3 of the BFI-SF recorded a participants' fatigue on a scale from 0 to 10. Higher scores indicated a higher severity of fatigue. An increase in score from baseline indicated a worsening of fatigue. A decrease in score from baseline indicated an improvement in fatigue.
Measured: Baseline and Week 8
Change From Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory - Short Form (BPI-SF)
Item 3 of the BPI-SF recorded a participants' pain on a scale from 1 to 10, where pain was mild (score of 1 to 4), moderate (score of 5 to 6), or severe (score of 7 to 10). An increase in score from baseline indicated a worsening of pain. A decrease in score from baseline indicates a lessening of pain.
Measured: Baseline and Week 8
Change From Baseline in Physical Functioning as Measured by the Physical Function Domain of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire - Core 30 Item (EORTC QLQ-C30)
The physical function domain of the EORTC QLQ-C30 assessed a participants' quality of life regarding their physical function on a scale from 1 to 4, with higher scores indicating a worse outcome. An increase in score from baseline indicated a worsening of physical functioning. A decrease in score from baseline indicated an improvement in physical functioning.
Measured: Baseline and Week 8
Change From Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30
Questions 29 and 30 of the EORTC QLQ-C30 assessed a participants' global health status on a scale from 1 to 7, with higher scores indicating a better outcome. An increase in score from baseline indicated an improvement in global health status. A decrease in score from baseline indicated a worsening in global health status.
Measured: Baseline and Week 8
Change From Baseline for All Subscales of the BFI-SF
The BFI-SF was a questionnaire that included 3 items to assess fatigue severity and 5 items to assess interference due to fatigue, with each item reported on a numeric rating scale from 0 to 10. Higher scores indicated a higher severity of fatigue. An increase in score from baseline indicated a worsening of fatigue. A decrease in score from baseline indicated an improvement in fatigue.
Measured: Baseline and Week 8
Change From Baseline for All Subscales of the BPI-SF
The BPI-SF was a 9-item questionnaire which included 2 body diagrams, four items to assess pain severity, four items to assess pain interference and one question about percentage of pain relief by analgesics. The level of pain and pain interference assessed could be divided into categories based on score of mild (1 to 4), moderate (5 to 6), and severe (7 to 10). An increase in score from baseline indicated a worsening of pain. A decrease in score from baseline indicated a lessening of pain.
Measured: Baseline and Week 8
Change From Baseline for All Subscales and Domains of EORTC QLQ-C30
The EORTC QLQ-C30 was a self-reporting 30-item generic instrument which assessed 5 functional domains (physical, role, emotional, cognitive, social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties), and a global health status/quality of life (QOL) scale. Higher scores indicated a worse outcome. An increase in score from baseline indicated a worsening of outcome. A decrease in score from baseline indicated an improvement in outcome.
Measured: Baseline and Week 8
Average Score of VAS Scores as Measured by EQ-5D-5L
The EQ-5D-5L questionnaire was a 2-page, standardized instrument for use as a measure of health outcome. It was comprised of a 5-dimension health status measure and a visual analogue scale. The 5-dimension health status measure evaluates: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The visual analogue scale recorded the participant's self-rated health on a vertical, visual analogue scale where the endpoints were labelled 'Best imaginable health state' and 'Worst imaginable health state'.
Measured: Baseline and Week 8
Average Score on Single Question on Symptom Bother GP5 From Functional Assessment of Cancer Therapy - General (FACT-G)
The GP5 from the FACT-G was a single item included in the Physical Well-Being subscale of the FACT-G. Responses to the item: "I am bothered by side effects of treatment" are rated on a 5-point Likert scale from "not at all" to "very much".
Measured: Approximately 2 years
Average Score of Patient Global Impression of Change (PGIC)
The PGIC scale consisted of one item which measures the participants' perception of change in their condition relative to the beginning of the trial. Responses are rated on a 7-item response scale ranging from very much improved to very much worse.
Measured: Approximately 2 years
Maximum Plasma Concentration (Cmax) of Sotorasib
Measured: Approximately 2 years
Cmax of Panitumumab
Measured: Approximately 2 years
Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib
Measured: Approximately 2 years
AUC of Panitumumab
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start19 Apr 2022
- Primary completion16 Jul 2025
- Study completion14 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05198934
- Sponsor's protocol ID
- 20190172
- Other IDs
- 2024-511187-81-00
- Acronym
- CodeBreak300
- Status last verified
- Jun 2026
- First submitted
- 6 Jan 2022
- Last updated
- 22 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 37870968Pietrantonio 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.
PubMed 40215429Modest 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.
PubMed 40812325Salvatore L, Fakih M, Kuboki Y, Hong DS, Modest DP, Taieb J, Price TJ, Cremolini C, Majer IM, Rehn M, Chan E, Chen Z, Tran Q, Pietrantonio F. Matching-Adjusted Indirect Comparison of Sotorasib Plus Panitumumab Versus Trifluridine/Tipiracil Plus Bevacizumab in Chemorefractory Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2026 Apr 23:S1533-0028(26)00026-5. doi: 10.1016/j.clcc.2026.04.003. Online ahead of print.
PubMed 42173791
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
- ClinicalTrials.gov ID
- NCT05198934
- Acronym / sponsor ID
- CodeBreak300 / 20190172
- Conditions
- Colorectal Cancer (CRC)
- Keywords
- Sotorasib, AMG 510, Panitumumab, Metastatic colorectal cancer, Kirsten rat sarcoma p.G12C mutation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 14 Apr 2026 (actual)
- First posted
- 20 Jan 2022 (actual)
- Results
- Posted 22 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Trifluridine and Tipiracil, Drug: RegorafenibParticipants will be administered trifluridine and tipiracil, or regorafenib |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (14 listed)
- 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:
- Leptomeningeal disease.
- Significant gastrointestinal (GI) disorder that results in significant malabsorption, requirement for intravenous (IV) alimentation, or inability to take oral medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SotorasibAlso: AMG 510, Lumakras, LumykrasSotorasib will be administered orally | Drug | Arm A: Sotorasib 960 mg QD + panitumumab, Arm B: Sotorasib 240 mg QD + panitumumab |
| PanitumumabAlso: VectibixPanitumumab will be administered as intravenous (IV) infusion | Drug | Arm A: Sotorasib 960 mg QD + panitumumab, Arm B: Sotorasib 240 mg QD + panitumumab |
| Trifluridine and TipiracilAlso: LonsurfTrifluridine and Tipiracil will be administered orally | Drug | Arm C : Investigator's choice |
| RegorafenibAlso: StivargaRegorafenib will be administered orally | Drug | Arm C : Investigator's choice |
Primary outcome
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by BICR
Time frame: From randomization until DCO or death; median (min, max) time on trial was 6.23 (0.1, 14.0) months
PFS was defined as time from randomization until disease progression or death from any cause, whichever occurred first, for all participants. Progression was assessed using RECIST v1.1 per BICR.
22 secondary outcomes
Overall Survival (OS)
Time frame: Approximately 3 years
Objective Response Rate (ORR) Per RECIST Version 1.1 as Assessed by BICR
Time frame: Approximately 3 years
Duration of Response (DOR) Per RECIST Version 1.1 as Assessed by BICR
Time frame: Approximately 3 years
Time to Response (TTR) as Assessed by BICR
Time frame: Approximately 3 years
Disease Control Rate (DCR) as Assessed by BICR
Time frame: Approximately 3 years
PFS Per RECIST Version 1.1 as Based on Investigator Assessment
Time frame: Approximately 3 years
ORR Per RECIST Version 1.1 as Based on Investigator Assessment
Time frame: Approximately 3 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Approximately 3 years
Change From Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory - Short Form (BFI-SF)
Time frame: Baseline and Week 8
Change From Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory - Short Form (BPI-SF)
Time frame: Baseline and Week 8
Change From Baseline in Physical Functioning as Measured by the Physical Function Domain of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire - Core 30 Item (EORTC QLQ-C30)
Time frame: Baseline and Week 8
Change From Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30
Time frame: Baseline and Week 8
Change From Baseline for All Subscales of the BFI-SF
Time frame: Baseline and Week 8
Change From Baseline for All Subscales of the BPI-SF
Time frame: Baseline and Week 8
Change From Baseline for All Subscales and Domains of EORTC QLQ-C30
Time frame: Baseline and Week 8
Average Score of VAS Scores as Measured by EQ-5D-5L
Time frame: Baseline and Week 8
Average Score on Single Question on Symptom Bother GP5 From Functional Assessment of Cancer Therapy - General (FACT-G)
Time frame: Approximately 2 years
Average Score of Patient Global Impression of Change (PGIC)
Time frame: Approximately 2 years
Maximum Plasma Concentration (Cmax) of Sotorasib
Time frame: Approximately 2 years
Cmax of Panitumumab
Time frame: Approximately 2 years
Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib
Time frame: Approximately 2 years
AUC of Panitumumab
Time frame: Approximately 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 37870968Fakih 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.
- Background: PubMed 40215429Pietrantonio 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.
- Background: PubMed 40812325Modest 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.
- Background: PubMed 42173791Salvatore L, Fakih M, Kuboki Y, Hong DS, Modest DP, Taieb J, Price TJ, Cremolini C, Majer IM, Rehn M, Chan E, Chen Z, Tran Q, Pietrantonio F. Matching-Adjusted Indirect Comparison of Sotorasib Plus Panitumumab Versus Trifluridine/Tipiracil Plus Bevacizumab in Chemorefractory Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2026 Apr 23:S1533-0028(26)00026-5. doi: 10.1016/j.clcc.2026.04.003. Online ahead of print.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
105 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sotorasib, Panitumumab and Trifluridine and Tipiracil in people with Colorectal Cancer (CRC), run by Amgen at 105 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 105 sites in Italy, United States, Japan, Spain, Greece and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by BICR (time frame: From randomization until DCO or death; median (min, max) time on trial was 6.23 (0.1, 14.0) months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05198934, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.