NCT05198934 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-07-22

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · NOT POSTED

Objective Response Rate (ORR) Per RECIST Version 1.1 as Assessed by BICR

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outcome · NOT POSTED

Duration of Response (DOR) Per RECIST Version 1.1 as Assessed by BICR

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outcome · NOT POSTED

Time to Response (TTR) as Assessed by BICR

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outcome · NOT POSTED

Disease Control Rate (DCR) as Assessed by BICR

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outcome · NOT POSTED

PFS Per RECIST Version 1.1 as Based on Investigator Assessment

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outcome · NOT POSTED

ORR Per RECIST Version 1.1 as Based on Investigator Assessment

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outcome · NOT POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · NOT POSTED

Change From Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory - Short Form (BFI-SF)

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outcome · NOT POSTED

Change From Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory - Short Form (BPI-SF)

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outcome · NOT POSTED

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)

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outcome · NOT POSTED

Change From Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30

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outcome · NOT POSTED

Change From Baseline for All Subscales of the BFI-SF

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outcome · NOT POSTED

Change From Baseline for All Subscales of the BPI-SF

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outcome · NOT POSTED

Change From Baseline for All Subscales and Domains of EORTC QLQ-C30

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outcome · NOT POSTED

Average Score of VAS Scores as Measured by EQ-5D-5L

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outcome · NOT POSTED

Average Score on Single Question on Symptom Bother GP5 From Functional Assessment of Cancer Therapy - General (FACT-G)

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outcome · NOT POSTED

Average Score of Patient Global Impression of Change (PGIC)

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outcome · NOT POSTED

Maximum Plasma Concentration (Cmax) of Sotorasib

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outcome · NOT POSTED

Cmax of Panitumumab

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outcome · NOT POSTED

Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib

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outcome · NOT POSTED

AUC of Panitumumab

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outcome · POSTED

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by BICR

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: Sotorasib
Drug: Panitumumab
label
Arm A: Sotorasib 960 mg QD + panitumumab
type
EXPERIMENTAL
intervention Names
Drug: Sotorasib
Drug: Panitumumab
label
Arm B: Sotorasib 240 mg QD + panitumumab
type
EXPERIMENTAL
description
Participants will be administered trifluridine and tipiracil, or regorafenib
intervention Names
Drug: Trifluridine and Tipiracil
Drug: Regorafenib
label
Arm C : Investigator's choice
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A: Sotorasib 960 mg QD + panitumumab
Arm B: Sotorasib 240 mg QD + panitumumab
description
Sotorasib will be administered orally
name
Sotorasib
other Names
AMG 510, Lumakras, Lumykras
type
DRUG
arm Group Labels
Arm A: Sotorasib 960 mg QD + panitumumab
Arm B: Sotorasib 240 mg QD + panitumumab
description
Panitumumab will be administered as intravenous (IV) infusion
name
Panitumumab
other Names
Vectibix
type
DRUG
arm Group Labels
Arm C : Investigator's choice
description
Trifluridine and Tipiracil will be administered orally
name
Trifluridine and Tipiracil
other Names
Lonsurf
type
DRUG
arm Group Labels
Arm C : Investigator's choice
description
Regorafenib will be administered orally
name
Regorafenib
other Names
Stivarga
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 160
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
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

secondary Outcomes

description
OS was defined as time from randomization until death from any cause.
measure
Overall Survival (OS)
time Frame
Approximately 3 years
description
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.
measure
Objective Response Rate (ORR) Per RECIST Version 1.1 as Assessed by BICR
time Frame
Approximately 3 years
description
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.
measure
Duration of Response (DOR) Per RECIST Version 1.1 as Assessed by BICR
time Frame
Approximately 3 years
description
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.
measure
Time to Response (TTR) as Assessed by BICR
time Frame
Approximately 3 years
description
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).
measure
Disease Control Rate (DCR) as Assessed by BICR
time Frame
Approximately 3 years
description
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.
measure
PFS Per RECIST Version 1.1 as Based on Investigator Assessment
time Frame
Approximately 3 years
description
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.
measure
ORR Per RECIST Version 1.1 as Based on Investigator Assessment
time Frame
Approximately 3 years
description
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.
measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
time Frame
Approximately 3 years
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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

Full study description

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).

Source references

references

citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
Salvatore 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.
pmid
42173791
type
BACKGROUND