A Study of ABT-165 in Subjects With Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABT-165, a Dual Variable Domain Immunoglobulin in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: paclitaxel
* Drug: FOLFIRI
* Drug: ABT-165
* Drug: ABBV-181


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical lab testing | Hematology, Chemistry, and Urinalysis | Up to 30 days after a 24-month treatment period | 
| 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 | Electrocardiogram (ECG), echocardiogram (ECHO), basic natriuretic peptide (BNP) and troponin I | Up to 30 days after a 24-month treatment period | 
| Area under the curve (AUC) form time zero to the last measurable concentration AUC (0-t) | AUC (0-t) = Area under the serum concentration versus time curve form time zero (pre-dose) to the time of the last measurable concentration | Up to 90 days after a 24-month treatment period | 
| Physical exam | Assessment of normal/abnormal physical findings | Up to 30 days after a 24-month treatment period | 
| Number of participants with Adverse Events | Collect all adverse events at each visit | Up to 90 days after a 24-month treatment period | 
| Vital signs | Blood pressure, heart rate, respiratory rate and body temperature | Up to 30 days after a 24-month treatment period | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABBV-181, ABT-165, cancer, neoplasm, advanced solid tumor, colorectal cancer