Advanced Solid Tumors with KRAS p.G12C Mutation
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For the full list of inclusion criteria please refer to section 5.1 of the of the subprotocols. All subprotocols Pathologically documented, locally-advanced or metastatic NSCLC (subprotocol F)/ metastatic NSCLC with active brain metastases (subprotocol G) / metastatic colorectal cancer (suprotocol H, Part 1 and Part 2 cohort A, D, E+F)/ metastatic advanced solid tumor (subprotocol H Part 2 Cohort B)/ metastatic NCSLC (subprotocol H, Part 2 Cohort C) 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 in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Measurable disease per RECIST 1.1 criteria (Section 11.8) 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 Subprotocol F •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 = ULN •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 •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 • Total bilirubin =1 x ULN for Part 1 Cohort B and Part 2 Cohort F 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 G: •Pathologically documented, metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing, and with active brain metastases. Subjects must have received anti-PD-1 or anti-programmed death-ligand 1 (PD-L1) immunotherapy (unless contraindicated) AND/OR platinum-based combination chemotherapy AND targeted therapy (if actionable oncogenic driver mutations were identified [eg; EGFR, ALK, and ROS1]), or if subject refused standard therapy. KRAS p.G12C mutation must be identified by an approved diagnostic device for detection of KRAS p.G12C in NSCLC or be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. •Metastatic brain disease meeting the following cri
Exclusion criteria
Exclusion criteria: 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) •Exclusion 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 •Has an active infection requiring systemic therapy •Received radiation therapy to the lung that is ? 30 Gy within 6 months of the first dose of trial treatment Subprotocols F and H: •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 Primary brain tumor •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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: All subprotocols Phase 1 To evaluate the safety and tolerability of investigational regimens of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors Phase 2 To evaluate tumor objective response rate (ORR) assessed by RECIST 1.1 criteria of investigational regimens of sotorasib in adult subjects with KRAS p.G12C mutated advanced tumors (non small-cell lung cancer [NSCLC], colorectal cancer [CRC], and other tumor types).;Secondary Objective: All subprotocols Phase 1 To characterize PK of product(s) used in investigational regimens of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors. To evaluate anti-tumor activity of investigational regimens of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors Phase 2 To evaluate other measures of efficacy of investigational regimens of sotorasib in adult subjects with KRAS p.G12C mutant advanced tumors by RECIST 1.1 (NSCLC, CRC, and other tumor types). To evaluate the safety and tolerability of investigational regimens of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors (NSCLC, CRC, and other tumor types). To evaluate the PK of sotorasib administered in investigational regimens;Primary end point(s): Dose-limiting toxicities, treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests;Timepoint(s) of evaluation of this end point: The primary analysis for this study will occur when target enrollment is complete and each subject either completes at least 6 months on study or withdraws from the study. The final analysis will be conducted and reported following the end of the study. The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic parameters of product(s) including, but not limited to, maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), and area under the plasma concentration-time curve (AUC) Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), measured by computed tomography (CT) or magnetic resonance imaging (MRI) and assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).;Timepoint(s) of evaluation of this end point: The primary analysis for this study will occur when target enrollment is complete and each subject either completes at least 6 months on study or withdraws from the study. The final analysis will be conducted and reported following the end of the study. The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study (eg, long-term follow-up), as applicable. | — |
Countries
Australia, Austria, Belgium, Canada, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen S.A.
Outcome results
None listed