Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma
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This is an open-label, Phase 1, dose escalation study of oral ARQ 092 administered to subjects with advanced solid tumors and recurrent malignant lymphoma. The study is designed to explore the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARQ 092 and to define a recommended Phase 2 dose of ARQ 092.
Subjects in this study will receive ARQ 092 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 10 mg every other day (QOD) and will escalate until the MTD or RP2D is determined. Cycles will be repeated in four-week (28 day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.
Assess the safety and tolerability of ARQ 092 in subjects with advanced solid tumors and recurrent malignant lymphoma by monitoring frequency and severity of adverse events [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks ]
Secondary Outcome Measures :
Assess the pharmacokinetic profile (Cmax, AUC, and half-life) of ARQ 092 [ Time Frame: During the first 29 days of treatment for each dose level ]
Assess pharmacodynamic activity [ Time Frame: During the first 29 days of treatment ]
Determine preliminary evidence of activity as defined by RECIST v 1.1 [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks ]
Determine recommended Phase 2 dose [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks ]
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Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Men or women ≥18 years old
Histologically or cytologically documented, incurable, locally advanced or metastatic solid tumors or recurrent malignant lymphoma in subjects who failed standard therapy or for whom standard or curative therapy does not exist or is not tolerable.
Evaluable or measurable disease
Life expectancy greater than three months
ECOG performance status ≤2
Hemoglobin (Hgb) ≥9.5 g/dl
Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
Platelet count ≥75 x 10^9/L
Total bilirubin ≤1.5 × upper limit of normal (ULN)
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 × ULN
Serum creatinine ≤1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for subjects with creatinine levels >1.5 x ULN
Agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug
History of Type 1 or 2 diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose ≥160 mg/dL at the prestudy visit. If a diabetic cohort is enrolled, only subjects with a medical history of controlled Type 1 or 2 diabetes mellitus will be enrolled in the cohort.
Grade 2 or worse hypercholesterolemia or hypertriglyceridemia or >8% glycated Hb (HbA1C)
Known brain metastases not radiographically stable for ≥3 months or leptomeningeal disease
History of myocardial infarction (MI) or NYHA Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 092 (MI occurring >6 months of the first dose of ARQ 092 will be permitted); Grade 2 or worse conduction defect (eg right or left bundle branch block); left ventricular ejection fraction (LVEF) < 50% assessed by echocardiogram/MUGA scan
Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of the first dose of ARQ 092 (within 2 weeks for orally administered drugs)
Major surgery within four weeks of the first dose of ARQ 092
Previous treatment with AKT inhibitors
Concurrent severe uncontrolled illness not related to cancer
Ongoing or active known infection, including human immunodeficiency virus (HIV) infection or bleeding
Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
Blood transfusion within 5 days prior to blood draw being used to confirm eligibility
Pregnant or breastfeeding
Previous other malignancy within 2 years prior to the first dose of ARQ 092, with the exception of carcinoma in-situ of the cervix, basal cell carcinoma and superficial bladder tumors curatively treated.