Master Protocol of Sotorasib (AMG 510) in Subjects with Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreaK 101)
- Conditions
- Advanced Solid Tumors with KRAS p.G12C MutationTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004721-23-AT
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1200
For the full list of inclusion criteria please refer to section 5.1 of the of the subprotocols.
All subprotocols
Measurable disease per RECIST 1.1 criteria
Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2
Life expectancy of > 3 months, in the opinion of the investigator
Ability to take oral medications and willing to record daily adherence to investigational product
Corrected QT interval (QTc) = 470 msec for women and = 450 msec for men (based on average of screening triplicates
Adequate hematological laboratory assessments, as follows:
•Absolute neutrophil count (ANC) = 1.5 x 109/L
•Platelet count = 100 x 109/L
•Hemoglobin = 9 g/dL
Adequate renal laboratory assessments, as follows:
•Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation = 60 ml/min/1.73 m2
•Adequate coagulation laboratory assessments as follows:
•PT or PTT or activated partial thromboplastin time = 1.5 x ULN, OR (INR) = 1.5 x ULN or within target range if on prophylactic anticoagulation therapy.
Subprotocol F
•Pathologically documented, locally-advanced or metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing. KRAS p.G12C mutation must be identified by an approved diagnostic device for detection of KRAS p.G12C in NSCLC or be performed according to in-country requirements.
•Adequate hepatic laboratory assessments, as follows:
•AST and ALT = 2.5 times the upper limit of normal (ULN), except if alkaline phosphatase > 2.5 times the ULN, then AST and/or ALT must be = 1.5 times the ULN
• Total bilirubin (TBL) = 1.5x ULN: for subjects with known Gilbert’s syndrome TBL = 2.0 x ULN will be allowed if AST, ALT and direct bilirubin are within normal limits
•Adequate coagulation laboratory assessments, as follows:
•Partial prothrombin time (PTT) or partial thromboplastin time (PTT) < 1.5 x ULN, OR international normalized ratio (INR) < 1.5 x ULN or within target range if on prophylactic anticoagulation therapy
Subprotocol H
•Pathologically documented, metastatic colorectal cancer with KRAS
p.G12C mutation identified through molecular testing performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)- certified laboratory.
•Subjects must not have required dose reduction or been intolerant of a KRAS G12C inhibitor if they have received treatment with a KRAS G12C inhibitor in the past. A minimum of 2 subjects must be KRAS G12C inhibitor naïve per dose level. (Part 1)
•Adequate hepatic laboratory assessments, as follows:
• AST =2.5 x ULN (if liver metastases are present, =5 x ULN)
• ALT = 2.5 x ULN (if liver metastases are present, = 5 x ULN)
•Total bilirubin = 1.5 x ULN for Part 1 Cohort A, Part 2 Cohorts A to E and Cohort H
•Total bilirubin =1 x ULN for Part 1 Cohort B and Part 2 Cohorts F, G and I
Subprotocol J:
• Pathologically documented, locally-advanced or metastatic malignancy with KRAS p.G12C mutation identified through molecular testing performed according to in country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600
For the full list of exclusion criteria please refer to section 5.2 of the of the subprotocols.
All sub protocols
•History or presence of hematological malignancies unless curatively treated with no evidence of disease = 2 years
History of other malignancy within the past 2 years, with the following exceptions:
-Malignancy treated with curative intent and with no known active disease present for >2 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.
•Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or cardiac arrythmia requiring medication
GI tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for IV alimentation, uncontrolled inflammatory GI disease (eg, Crohn’s disease, ulcerative colitis)
•Evidence of hepatitis infection based on the following results and/or criteria:
-Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B or recent acute hepatitis B)
-Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [anti-HBs] testing is necessary. Undetectable anti-HBs in this setting would suggest unclear and possible infection and needs exclusion).
-Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction (PCR) is necessary. Detectable Hepatitis C virus RNA suggests chronic hepatitis C
-Known positive test for HIV
Subprotocols F,H,J:
•Active brain metastases and/or carcinomatous meningitis from non-brain tumors. 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 following criteria: a) residual neurological symptoms grade = 2; b) on stable doses of dexamethasone, if applicable; and c) follow-up MRI performed within 30 days shows no new lesions appearing
Sub protocol H,J:
Primary brain tumor
Sub protocol H:
•History of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis
•Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose =1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
•Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy [except for subjects with history of breast cancer receiving adjuvant hormonal therapy], or investigational agent except for sotorasib) within 28 days of study day 1. Targeted small molecule inhibitors, within 14 days of study day 1, provided at least 5 half lives have passed.
•Currently receiving treatment in another investigational device or drug study, or less than 28 days since last intervention on another investigational device or drug study(ies) with the exception of sotorasib studies, in which case, there is no requirement
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method