Advanced Solid Tumors
Conditions
Keywords
ABBV-181, ABT-165, cancer, neoplasm, advanced solid tumor, colorectal cancer
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.
Interventions
DRUGpaclitaxel
Paclitaxel will be administered by intravenous infusion.
DRUGFOLFIRI
5-fluorouracil, Folinic acid and Irinotecan will be administered by intravenous infusion.
DRUGABT-165
ABT-165 will be administered by intravenous infusion at escalating dose levels.
DRUGABBV-181
ABBV-181 will be administered by intravenous infusion.
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vital signs | Up to 30 days after a 24-month treatment period | Blood pressure, heart rate, respiratory rate and body temperature |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Outcome results
None listed