Clinical trial NCT01946074: A Study of ABT-165 in Subjects With Solid Tumors
Official title: A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABT-165, a Dual Variable Domain Immunoglobulin in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: ABBV-181
ABT-165
cancer
neoplasm
advanced solid tumor
colorectal cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2013-09-19
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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-165.
* 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.

Primary outcomes:
measure: Clinical lab testing
timeFrame: Up to 30 days after a 24-month treatment period
measure: Maximum observed serum concentration (Cmax) of ABT-165
timeFrame: Up to 90 days after a 24-month of treatment period
measure: The terminal elimination half life of ABT-165
timeFrame: Up to 90 days after a 24-month treatment period
measure: Cardiac assessment
timeFrame: Up to 30 days after a 24-month treatment period
measure: Area under the curve (AUC) form time zero to the last measurable concentration AUC (0-t)
timeFrame: Up to 90 days after a 24-month treatment period
measure: Physical exam
timeFrame: Up to 30 days after a 24-month treatment period
measure: Number of participants with Adverse Events
timeFrame: Up to 90 days after a 24-month treatment period
measure: Vital signs
timeFrame: Up to 30 days after a 24-month treatment period
Secondary outcomes:
measure: Duration of overall response (DOR)
timeFrame: Up to 30 days after a 24-month treatment period
measure: Objective response rate (ORR)
timeFrame: Up to 30 days after a 24-month treatment period
measure: Progression free survival (PFS)
timeFrame: Up to 30 days after a 24-month treatment period
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Pima /ID# 105677
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare /ID# 105678
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 141389
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 141164
state: California
city: Stanford
country: United States
facility: Stanford University School of Med /ID# 123758
state: California
city: Peoria
country: United States
facility: Illinois Cancer Care, PC /ID# 151970
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Research Center /ID# 138022
state: Indiana
city: Durham
country: United States
facility: Duke Cancer Center /ID# 105679
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville Centennial /ID# 143280
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research /ID# 123757
state: Texas
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Gordon MS, Nemunaitis J, Barve M, Wainberg ZA, Hamilton EP, Ramanathan RK, Sledge GW Jr, Yue H, Morgan-Lappe SE, Blaney M, Kasichayanula S, Motwani M, Wang L, Naumovski L, Strickler JH. Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors. Mol Cancer Ther. 2021 Oct;20(10):1988-1995. doi: 10.1158/1535-7163.MCT-20-0985. Epub 2021 Jul 26.