Previously Treated Metastatic Colorectal Cancer Subjects with KRAS p.G12C Mutation MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Sotorasib
Product Code: AMG 510
Pharmaceutical Form: Tablet
INN or Proposed INN: Sotorasib
Current Sponsor code: AMG 510
Concentration unit: mg milligram(s)
Concentration type: equal
Con
Sponsors
Amgen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 101Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures. 102Age = 18 years 103Pathologically documented metastatic colorectal adenocarcinoma with KRAS p.G12C mutation as determined by central testing 104Subjects 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. 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 105Subjects 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. 106Measurable disease per RECIST 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation. 107Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2 108Life expectancy of > 3 months, in the opinion of the investigator 109Adequate hematologic and end-organ function, defined as the following within 10 days prior to randomization: Absolute neutrophil count (ANC) = 1.5 x 109/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 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility) Aspartate aminotransferase (AST) and ALT = 2.5 times the upper limit of normal (ULN) Serum bilirubin = 1.0 x ULN. For subjects with Gilbert’s disease, direct bilirubin = 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) calc
Exclusion criteria
Exclusion criteria: 201Active 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 if they meet all of the criteria specified in the protocol 202History or presence of hematological malignancies unless curatively treated with no evidence of disease 2 years 203History of other malignancy within the past 3 years, with exceptions specified in the protocol 204Leptomeningeal disease 205Significant GI disorder that results in significant malabsorption, requirement for IV alimentation, or inability to take oral medication 206History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis 207Significant 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 208Significant uncontrolled concomitant disease that could affect compliance with protocol procedures or interpretation of results or that pose a risk to subject safety, in the opinion of the investigator or Amgen medical monitor 209Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Subjects with PleurX catheters or intraperitoneal drainage catheters in place may be considered for the study with Medical Monitor approval. 210Known history of human immunodeficiency virus infection 211Exclusion 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 212Subjects have received both trifluridine and tipiracil and regorafenib in the past 213Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exceptions of alopecia (any grade allowed), neuropathy (up to grade 2 allowed), or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 6 months), or endocrine adverse events that are stably maintained on appropriate replacement therapy 214Previous treatment with a KRAS G12C inhibitor 215Prior treatment with trifluridine and tipiracil in those subjects where investigator’s choice would be trifluridine and tipiracil 216Prior treatment with regorafenib in those subjects where investigator’s choice would be regorafenib 217Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity to CTCAE version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia allowed). 218Anti-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 bisphosphona
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To compare progression free 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);Secondary Objective: Key Secondary •To compare overall survival (OS) in previously treated subjects with KRAS p.G12C mutated CRC receiving sotorasib 240 mg 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) •To evaluate efficacy of sotorasib 240 mg 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), as assessed by: •Objective response rate (ORR);Primary end point(s): •Progression Free Survival (PFS) – defined as time from randomization until disease progression or death from any cause, whichever occurs first, for all subjects. Progression unless noted otherwise, use Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per Blinded Independent Central Review (BICR);Timepoint(s) of evaluation of this end point: PFS - will be event driven and occur when approximately 60 PFS events have been observed from the sotorasib 960 mg and panitumumab arm and the investigator’s choice arm. The PFS primary analysis may be delayed to ensure that the enrollment is finished and the delayed primary analysis will be triggered when the last randomized subject has had the opportunity to have at least 8 weeks of follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary •Overall survival (OS) - defined as time from randomization until death from any cause •Objective response rate (ORR) = 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.;Timepoint(s) of evaluation of this end point: OS - at the 960 mg dose level for the combination treatment group of sotorasib and panitumumab versus the control group will occur when PFS is claimed statistically significant at primary analysis at the 960 mg dose level or at both the 960 mg and 240 mg dose levels. The primary analysis of OS at the 240 mg dose level will occur when the primary analysis of OS at the 960 mg dose level is claimed statistically significant. ORR - for the combination treatment group of sotorasib and panitumumab versus the control group at either 960 mg or 240 mg dose level will occur when both PFS and OS are claimed statistically significant at primary analysis at this dose level. | — |
Countries
Australia, Greece, Korea, Republic of, Mexico, Spain, Taiwan, United Kingdom
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen S.A.
Outcome results
None listed