Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma

A Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Tumor; Malignant Lymphoma
• Intervention / Treatment: Drug: ARQ 092

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arizona
    • Scottsdale, Arizona, United States, 85258
  • Florida
    • Miami, Florida, United States, 33136
  • Georgia
    • Atlanta, Georgia, United States, 30322
    • Atlanta, Georgia, United States, 30341
  • Indiana
    • Lafayette, Indiana, United States, 47905
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women ≥18 years old
2. 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.
3. Evaluable or measurable disease
4. Life expectancy greater than three months
5. ECOG performance status ≤2
6. Hemoglobin (Hgb) ≥9.5 g/dl
7. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
8. Platelet count ≥75 x 10^9/L
9. Total bilirubin ≤1.5 × upper limit of normal (ULN)
10. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 × ULN
11. 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
12. Agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug

Exclusion Criteria:

1. 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.
2. Grade 2 or worse hypercholesterolemia or hypertriglyceridemia or >8% glycated Hb (HbA1C)
3. Malabsorption syndrome
4. Known brain metastases not radiographically stable for ≥3 months or leptomeningeal disease
5. 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
6. 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)
7. Major surgery within four weeks of the first dose of ARQ 092
8. Previous treatment with AKT inhibitors
9. Concurrent severe uncontrolled illness not related to cancer
10. Ongoing or active known infection, including human immunodeficiency virus (HIV) infection or bleeding
11. Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
12. Blood transfusion within 5 days prior to blood draw being used to confirm eligibility
13. Pregnant or breastfeeding
14. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess the pharmacokinetic profile (Cmax, AUC, and half-life) of ARQ 092	During the first 29 days of treatment for each dose level
Assess pharmacodynamic activity	During the first 29 days of treatment
Determine preliminary evidence of activity as defined by RECIST v 1.1	Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks
Determine recommended Phase 2 dose	Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks

Collaborators and Investigators

• Sponsor: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): July 6, 2017
• Study Completion (Actual): August 7, 2017

Study Registration Dates

• First Submitted: November 10, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Actual): October 23, 2017
• Last Update Submitted That Met QC Criteria: October 19, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Biomarker; Lymphoma; Targeted therapy; Phase 1; Phase I; Endometrial cancer; Tumor; Molecular therapy; mTOR inhibitor; Tumour; PI3K inhibitor; AKT; Clinical oncology; AKT1; AKT inhibitor; ARQ 092; AKT pathway; AKT signaling; AKT pan inhibitor; AKT2; AKT3; AKT1 mutation; AKT1-E17K; AKT1-E17K mutation; AKT 2 inhibitor; AKT 3 inhibitor; AKT 3 amplification; PI3K AKT mTOR signalling pathway; PIK3CA H1047R mutation
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms; Lymphoma
• Other Study ID Numbers: ARQ 092-101