A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABT-165, a Dual Variable Domain Immunoglobulin in Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- FOLFIRI
- Conditions
- Advanced Solid Tumors
- Sponsor
- AbbVie
- Enrollment
- 101
- Locations
- 10
- Primary Endpoint
- Clinical lab testing
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-165 when administered as monotherapy and in combination with paclitaxel or 5-fluoruracil, folinic acid and irinotecan (FOLFIRI) or ABBV-181 with/without paclitaxel in subjects with advanced solid tumors. Enrollment to Cohorts A, B were completed and for Cohorts C and D are recruiting.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must have advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
- •Subject has adequate bone marrow, renal, hepatic and coagulation function.
- •Subject must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or disease evaluable by assessment of tumor antigens including but not limited to cancer antigen (CA-125) and prostate-specific antigen (PSA).
- •Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline prior to the first dose of study drug. Female subject considered not of childbearing potential must be documented as being surgically sterile or post-menopausal for at least 1 year. Women of childbearing potential and men must agree to use adequate contraception.
- •Subjects in the combination therapy cohorts must meet the above inclusion criteria and be eligible to receive paclitaxel or FOLFIRI per most current prescribing information, or at the discretion of the Investigator. Subjects in the combination therapy cohorts who are to receive ABBV-181, an anti-PD1 antibody, must also meet other criteria described in the Protocol.
Exclusion Criteria
- •Subject has received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or anti-cancer herbal therapy within 7 days prior to Cycle 1 Day 1 of ABT-
- •Subject has uncontrolled metastases to the central nervous system (CNS).
- •Subject has unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher.
- •Subject has history (within previous 5 years) of clinically significant pulmonary hypertension, uncontrolled systemic hypertension or hypertensive crisis, symptomatic heart failure, cardiomyopathy, myocardial infarction, unstable/severe angina pectoris, cardiac arrhythmia requiring medication, coronary/peripheral artery bypass graft, aneurysm or aneurysm repair, angioplasty, cerebrovascular accident, transient ischemic attack or the left ventricular ejection fraction (LVEF) less than 50%.
- •Subjects enrolled on the combination therapy phase must not meet the above exclusion criteria and must be eligible to receive paclitaxel or FOLFIRI per most current prescribing information, or at the discretion of the Investigator. Subjects receiving ABBV-181 must not meet other exclusion criteria described in the Protocol.
Arms & Interventions
Cohort B
ABT-165 plus FOLFIRI
Intervention: FOLFIRI
Monotherapy
ABT-165 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Additional subjects will be enrolled in an expansion cohort that will further evaluate ABT-165
Intervention: ABT-165
Cohort A
ABT-165 plus paclitaxel
Intervention: paclitaxel
Cohort A
ABT-165 plus paclitaxel
Intervention: ABT-165
Cohort B
ABT-165 plus FOLFIRI
Intervention: ABT-165
Cohort C
ABT-165 plus ABBV-181
Intervention: ABT-165
Cohort C
ABT-165 plus ABBV-181
Intervention: ABBV-181
Cohort D
ABT-165 plus ABBV-181 plus paclitaxel
Intervention: paclitaxel
Cohort D
ABT-165 plus ABBV-181 plus paclitaxel
Intervention: ABT-165
Cohort D
ABT-165 plus ABBV-181 plus paclitaxel
Intervention: ABBV-181
Outcomes
Primary Outcomes
Clinical lab testing
Time Frame: Up to 30 days after a 24-month treatment period
Hematology, Chemistry, and Urinalysis
The terminal elimination half life of ABT-165
Time Frame: Up to 90 days after a 24-month treatment period
Area under the curve (AUC) form time zero to the last measurable concentration AUC (0-t)
Time Frame: Up to 90 days after a 24-month treatment period
AUC (0-t) = Area under the serum concentration versus time curve form time zero (pre-dose) to the time of the last measurable concentration
Cardiac assessment
Time Frame: Up to 30 days after a 24-month treatment period
Electrocardiogram (ECG), echocardiogram (ECHO), basic natriuretic peptide (BNP) and troponin I
Physical exam
Time Frame: Up to 30 days after a 24-month treatment period
Assessment of normal/abnormal physical findings
Maximum observed serum concentration (Cmax) of ABT-165
Time Frame: Up to 90 days after a 24-month of treatment period
Number of participants with Adverse Events
Time Frame: Up to 90 days after a 24-month treatment period
Collect all adverse events at each visit
Vital signs
Time Frame: Up to 30 days after a 24-month treatment period
Blood pressure, heart rate, respiratory rate and body temperature
Secondary Outcomes
- Progression free survival (PFS)(Up to 30 days after a 24-month treatment period)
- Duration of overall response (DOR)(Up to 30 days after a 24-month treatment period)
- Objective response rate (ORR)(Up to 30 days after a 24-month treatment period)