A Study of ABT-165 in Subjects With Solid Tumors

Sponsor

AbbVie (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01946074

Collaborator

(none)

101

Enrollment

Locations

Arms

121.6

Anticipated Duration (Months)

10.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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, C and D is completed.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: paclitaxel Drug: FOLFIRI Drug: ABT-165 Drug: ABBV-181	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

101 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 8, 2013

Anticipated Primary Completion Date :

Sep 26, 2023

Anticipated Study Completion Date :

Sep 26, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort D ABT-165 plus ABBV-181 plus paclitaxel	Drug: paclitaxel Paclitaxel will be administered by intravenous infusion. Drug: ABT-165 ABT-165 will be administered by intravenous infusion at escalating dose levels. Drug: ABBV-181 ABBV-181 will be administered by intravenous infusion.
Experimental: Cohort C ABT-165 plus ABBV-181	Drug: ABT-165 ABT-165 will be administered by intravenous infusion at escalating dose levels. Drug: ABBV-181 ABBV-181 will be administered by intravenous infusion.
Experimental: Cohort B ABT-165 plus FOLFIRI	Drug: FOLFIRI 5-fluorouracil, Folinic acid and Irinotecan will be administered by intravenous infusion. Drug: ABT-165 ABT-165 will be administered by intravenous infusion at escalating dose levels.
Experimental: Cohort A ABT-165 plus paclitaxel	Drug: paclitaxel Paclitaxel will be administered by intravenous infusion. Drug: ABT-165 ABT-165 will be administered by intravenous infusion at escalating dose levels.
Experimental: 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	Drug: ABT-165 ABT-165 will be administered by intravenous infusion at escalating dose levels.

Outcome Measures

Primary Outcome Measures

Clinical lab testing [Up to 30 days after a 24-month treatment period]
Hematology, Chemistry, and Urinalysis
Maximum observed serum concentration (Cmax) of ABT-165 [Up to 90 days after a 24-month of treatment period]
The terminal elimination half life of ABT-165 [Up to 90 days after a 24-month treatment period]
Cardiac assessment [Up to 30 days after a 24-month treatment period]
Electrocardiogram (ECG), echocardiogram (ECHO), basic natriuretic peptide (BNP) and troponin I
Area under the curve (AUC) form time zero to the last measurable concentration AUC (0-t) [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
Physical exam [Up to 30 days after a 24-month treatment period]
Assessment of normal/abnormal physical findings
Number of participants with Adverse Events [Up to 90 days after a 24-month treatment period]
Collect all adverse events at each visit
Vital signs [Up to 30 days after a 24-month treatment period]
Blood pressure, heart rate, respiratory rate and body temperature

Secondary Outcome Measures

Duration of overall response (DOR) [Up to 30 days after a 24-month treatment period]
DOR is defined as the time from the subject's initial CR or PR to the time of disease progression
Objective response rate (ORR) [Up to 30 days after a 24-month treatment period]
ORR is defined as the proportion of the subjects who have a complete response (CR) or partial response (PR)
Progression free survival (PFS) [Up to 30 days after a 24-month treatment period]
PFS is defined as the time from the first dose date of ABT-165 to either disease progression or death, whichever occurs first

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute - Pima /ID# 105677	Scottsdale	Arizona	United States	85258-2345
2	Scottsdale Healthcare /ID# 105678	Scottsdale	Arizona	United States	85258-4566
3	University of California, Los Angeles /ID# 141389	Los Angeles	California	United States	90095
4	University of California, Davis Comprehensive Cancer Center /ID# 141164	Sacramento	California	United States	95817
5	Stanford University School of Med /ID# 123758	Stanford	California	United States	94305-2200
6	Illinois Cancer Care, PC /ID# 151970	Peoria	Illinois	United States	61615
7	Horizon Oncology Research Center /ID# 138022	Lafayette	Indiana	United States	47905
8	Duke Cancer Center /ID# 105679	Durham	North Carolina	United States	27710-3000
9	Tennessee Oncology-Nashville Centennial /ID# 143280	Nashville	Tennessee	United States	37203-1632
10	Mary Crowley Cancer Research /ID# 123757	Dallas	Texas	United States	75230