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

Phase 3

Active, not recruiting

• Conditions: Colorectal Cancer (CRC)
• Interventions: Drug: Trifluridine and Tipiracil; Drug: Sotorasib; Drug: Panitumumab; Drug: Regorafenib

• Registration Number: NCT05198934
• Lead Sponsor: Amgen

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-06
• Study First Submitted QC: 2022-01-06
• Study First Posted: 2022-01-20
• Study Start: 2022-04-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-15
• Primary Completion: 2025-07-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C : Investigator's choice	Trifluridine and Tipiracil	Participants will be administered trifluridine and tipiracil, or regorafenib
Arm B: Sotorasib 240 mg QD + panitumumab	Sotorasib	-
Arm A: Sotorasib 960 mg QD + panitumumab	Sotorasib	-
Arm A: Sotorasib 960 mg QD + panitumumab	Panitumumab	-
Arm B: Sotorasib 240 mg QD + panitumumab	Panitumumab	-
Arm C : Investigator's choice	Regorafenib	Participants will be administered trifluridine and tipiracil, or regorafenib

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Approximately 3 years

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Approximately 3 years
Change from Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30	Baseline and Week 8	Questions 29 and 30 of the EORTC QLQ-C30 assess 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 indicates an improvement in global health status. A decrease in score from baseline indicates a worsening in global health status.
Change from Baseline For All Subscales of the BPI	Baseline and Week 8	The BPI is a 9-item questionnaire which includes 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 can 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 indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.
Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib	Day 1 to approximately 2 years
Time to Response (TTR)	Approximately 3 years
Change from Baseline For All Subscales and Domains of EORTC QLQ-C30	Baseline and Week 8	The EORTC QLQ-C30 is a self-reporting 30-item generic instrument which assesses 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 indicate a worse outcome. An increase in score from baseline indicates a worsening of outcome. A decrease in score from baseline indicates an improvement in outcome.
Overall Survival (OS)	Approximately 3 years
Investigator Assessed ORR	Approximately 3 years
Change from Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory (BFI)	Baseline and Week 8	Item 3 of the BFI records a participants' fatigue on a scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.
AUC of Panitumumab	Day 1 to approximately 2 years
Change from Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory (BPI)	Baseline and Week 8	Item 3 of the BPI records a participants' pain on a scale from 1 to 10, where pain is 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 indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.
Change from Baseline For All Subscales of the BFI	Baseline and Week 8	The BFI is a questionnaire that includes 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 indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.
Change from Baseline in Visual Analog Scale (VAS) Scores as Measured by EuroQol-5D level 5 (EQ-5D-5L)	Baseline and Week 8	The EQ-5D-5L questionnaire is a 2-page, standardized instrument for use as a measure of health outcome. It is 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 records the participant's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.
Average Score on Single Question on Symptom Bother GP5 from Functional Assessment of Cancer Therapy - General (FACT-G)	Approximately 2 years	The GP5 from the FACT-G is 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".
Maximum Plasma Concentration (Cmax) of Sotorasib	Day 1 to approximately 2 years
Duration of Response (DOR)	Approximately 3 years
Disease Control Rate (DCR)	Approximately 3 years
Number of Participants with a Treatment-emergent Adverse Event (TEAE)	Approximately 3 years	A TEAE is any untoward medical occurrence in a clinical study participant following first dose of treatment irrespective of a causal relationship with the study treatment. Any clinically significant changes in vital signs and clinical laboratory tests following first dose will be recorded as TEAEs.
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 Questionnaire (EORTC QLQ-C30)	Baseline and Week 8	The physical function domain of the EORTC QLQ-C30 assesses 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 indicates a worsening of physical functioning. A decrease in score from baseline indicates an improvement in physical functioning.
Average Score of Patient Global Impression of Change (PGIC)	Approximately 2 years	The PGIC scale consists of one item which measures the participants' perception of change in their condition relative to the beginning of the study. Responses are rated on a 7-item response scale ranging from very much improved to very much worse.
Cmax of Panitumumab	Day 1 to approximately 2 years
Investigator Assessed PFS	Approximately 3 years

Trial Locations

Locations (103)

Central Alabama Research; 🇺🇸 Birmingham, Alabama, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

University of California Irvine; 🇺🇸 Orange, California, United States

Johns Hopkins University School of Medicine; 🇺🇸 Washington, District of Columbia, United States

Cancer Specialists of North Florida; 🇺🇸 Jacksonville, Florida, United States

Lakes Research LLC; 🇺🇸 Miami Lakes, Florida, United States

Northwest Georgia Oncology Centers PC; 🇺🇸 Marietta, Georgia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Revive Research Institute; 🇺🇸 Sterling Heights, Michigan, United States

Sparrow Clinical Research Institute; 🇺🇸 Lansing, Michigan, United States

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