2024-511187-81-00
Completed
Phase 3
A Phase 3 Multicenter, Randomized, Openlabel, 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 KRAS p.G12C Mutation
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Amgen Inc.
- Enrollment
- 99
- Locations
- 21
- Primary Endpoint
- PFS – defined as time from randomization until disease progression or death from any cause, whichever occurs first, for all subjects. Progression will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per Blinded Independent Central Review (BICR)
Overview
Brief Summary
To compare progressionfree survival (PFS) in previously treated subjects with 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
- Allocation
- Randomized
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
- •Fridericia's Correction Formula (QTcF) ≤ 470 msec
- •Ability to take oral medications and willing to record daily adherence to investigational product.
- •Age ≥ 18 years.
- •Pathologically documented metastatic colorectal adenocarcinoma with KRAS p.G12C mutation as determined by prospective central testing, using the analytically validated Qiagen Therascreen KRAS RGQ polymerase chain reaction (PCR) 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.
- •Subjects will have received at least 1 prior line of therapy for metastatic disease. Subjects must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless the subject, in the opinion of the investigator, is not a candidate for fluoropyrimidine, irinotecan, or oxaliplatin, in which case, the subject may be eligible after investigator discussion with Amgen medical monitor provided subject 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 subject. Notes: Subjects with tumors known to be MSI-H must have received prior checkpoint inhibitor therapy if available in the region unless there is a medical contraindication, in which case, the subject may be eligible after investigator discussion with Amgen medical monitor. Subjects with tumors known to have BRAF V600E mutation must have received prior treatment with encorafenib and cetuximab if available for this indication in the country or region unless there is a medical contraindication in the opinion of the investigator, in which case the subject may be eligible for the trial after investigator discussion with and approval of the Amgen medical monitor. Adjuvant therapy will count as a line of therapy for metastatic disease if the subject progressed on or within six months of completion of adjuvant therapy administration. Maintenance therapy is not considered as a separate regimen of therapy. Adjuvant therapy given after resection of metastatic disease counts as a line of therapy for metastatic disease. Perioperative chemotherapy with or without chemoradiation in the metastatic setting will count as one line of therapy for metastatic disease if that was part of a multidisciplinary treatment plan for surgery.
- •Subjects must be willing to provide archived tumor tissue samples (formalin-fixed paraffin-embedded [FFPE] sample collected within 5 years) or agree to undergo a pretreatment tumor biopsy (excisional or core biopsy) prior to enrollment.
- •Measurable disease per 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
Exclusion Criteria
- •Active brain metastases. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible
- •Known history of human immunodeficiency virus infection
- •Exclusion of hepatitis infection based on the following results and/or criteria: a)Positive hepatitis B surface antigen b)Negative HepBsAg with a positive for hepatitis B core antibody c)Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction is necessary. Detectable Hepatitis C virus RNA renders the subject ineligible. If above antibody/antigen testing is not able to be obtained, positive hepatitis B or C viral load
- •Subjects have received both trifluridine and tipiracil and regorafenib in the past
- •Unresolved toxicities from prior anti-tumor therapy
- •Previous treatment with a KRAS G12C inhibitor
- •Prior treatment with trifluridine and tipiracil in those subjects where investigator's choice would be trifluridine and tipiracil
- •Prior treatment with regorafenib in those subjects where investigator's choice would be regorafenib
- •Therapeutic or palliative radiation therapy within 2 weeks of study day 1
- •Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy [except for subjects with history of completely resected breast cancer with no active disease for over 3 years on long term adjuvant endocrine therapy], or investigational agent) within 4 weeks of study day 1; please note that bisphosphonates or anti-RANKL antibody therapy is allowed if needed for management of hypercalcemia or for prevention of skeletal events. Checkpoint inhibitor therapy within 6 weeks of study day 1 is also excluded
Arms & Interventions
Vectibix 20 mg/ml concentrate for solution for infusion, Vectibix 20 mg/ml concentrate for solution for infusion
Test
Intervention: Vectibix 20 mg/ml concentrate for solution for infusion (Drug)
SOTORASIB
Test
Intervention: SOTORASIB (Drug)
Stivarga 40 mg film-coated tablets, Stivarga 40 mg film-coated tablets
Comparator
Intervention: Stivarga 40 mg film-coated tablets (Drug)
Lonsurf 20 mg/8.19 mg film-coated tablets, Lonsurf 15 mg/6.14 mg film-coated tablets
Comparator
Intervention: Lonsurf 20 mg/8.19 mg film-coated tablets (Drug)
Lonsurf 20 mg/8.19 mg film-coated tablets, Lonsurf 15 mg/6.14 mg film-coated tablets
Comparator
Intervention: Lonsurf 15 mg/6.14 mg film-coated tablets (Drug)
Outcomes
Primary Outcomes
PFS – defined as time from randomization until disease progression or death from any cause, whichever occurs first, for all subjects. Progression will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per Blinded Independent Central Review (BICR)
PFS – defined as time from randomization until disease progression or death from any cause, whichever occurs first, for all subjects. Progression will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per Blinded Independent Central Review (BICR)
Secondary Outcomes
- Pharmacokinetic (PK) parameters of sotorasib and panitumumab including, but not limited to, maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC)
- Overall survival - defined as time from randomization until death from any cause
- Objective response = complete response (CR) + partial response (PR), assessed per RECIST 1.1. Response will be assessed by BICR. CR and PR require confirmatory repeat assessment at least 4 weeks after the first detection of response
- Incidence and severity of treatmentemergent adverse events, changes in vital signs, and changes in clinical laboratory tests
- Change from baseline over time to week 8 Fatigue severity measured by item 3 on the brief faigure invetory
- Change from baseline over time to 8 weeks for the BFI, BPI and EORTC QLQ-C30. Summary scores and changes from baseline of VAS scores as measured by EuroQol-5D level 5. Summary scores on symptom bother on GP5 from FACT-G. Summary scores of Patient Global Impression of change at each timepoint.
- Duration of overall response - defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first. Progression will be based on BICR per RECIST 1.1
Investigators
Medical Information
Scientific
Amgen Inc.
Study Sites (21)
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