A Study of ABT-165 in Subjects With Solid Tumors

AbbVie

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: paclitaxel; Drug: FOLFIRI; Drug: ABT-165; Drug: ABBV-181

Study type: Interventional

Funder types: Industry

Identifiers

NCT01946074

M14-006

Details and patient eligibility

About

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.

Enrollment: 101 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

101 participants in 5 patient groups

Monotherapy

Experimental group

Description:

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

Treatment:

Drug: ABT-165

Cohort A

Experimental group

Description:

ABT-165 plus paclitaxel

Treatment:

Drug: paclitaxel

Drug: ABT-165

Cohort B

Experimental group

Description:

ABT-165 plus FOLFIRI

Treatment:

Drug: FOLFIRI

Drug: ABT-165

Cohort C

Experimental group

Description:

ABT-165 plus ABBV-181

Treatment:

Drug: ABT-165

Drug: ABBV-181

Cohort D

Experimental group

Description:

ABT-165 plus ABBV-181 plus paclitaxel

Treatment:

Drug: paclitaxel

Drug: ABT-165

Drug: ABBV-181