A Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)
- Conditions
- Advanced Solid Tumors Cancer
- Interventions
- Drug: ABBV-176
- Registration Number
- NCT03145909
- Lead Sponsor
- AbbVie
- Brief Summary
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-176 for participants with advanced solid tumors likely to express Prolactin Receptor (PRLR). The study will consist of 2 cohorts: Dose Escalation and Expanded Recommended Phase 2 Dose.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
- Participant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies.
- Dose Escalation Cohort: must have breast cancer, colorectal cancer, adrenocortical carcinoma, chromophobe renal cell carcinoma.
- Expanded Cohort: must have breast cancer.
- Participant must consent to provide the following for biomarker analyses:
- Dose Escalation Cohort: archived tumor tissue or fresh tumor biopsy.
- Expanded Cohort: archived tumor tissue and fresh tumor biopsy.
- Participant has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Participant has adequate bone marrow, renal, and hepatic function.
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Participant received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic, or any investigational therapy within 21 days before Study Day 1; participant received palliative radiotherapy or small molecule targeted anti-cancer agents within 14 days of Study Day 1.
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Participant has prior exposure to any pyrrolobenzodiazopine-containing agent
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Participant has unresolved, clinically significant toxicities from prior anticancer therapy, defined as greater than Grade 1 on Common Terminology for adverse events.
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Participant has clinically significant uncontrolled conditions.
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Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG).
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Participant has received more than 4 prior lines of systemic cytotoxic therapy (not including neo-adjuvant or adjuvant therapy).
- For prior cytotoxic therapy, treatment for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy.
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Participant has a history of >= grade 3 AST, ALT, or bilirubin increase or has extensive liver resection (i.e., left lobe resection).
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Participant has a history of cholecystitis (subject with history of cholecystectomy will not be excluded), or has active gallbladder disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Expanded RPTD Cohort ABBV-176 ABBV-176 via intravenous administration in participants with breast cancer at the Recommended Phase Two Dose (RPTD) determined during the Dose Escalation Cohort Dose Escalation Cohort ABBV-176 ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached.
- Primary Outcome Measures
Name Time Method Dose Escalation Cohort: AUC∞ for ABBV-176 Up to approximately 57 days AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.
Dose Escalation Cohort: Tmax of ABBV-176 Up to approximately 57 days Time to Cmax (Tmax) of ABBV-176
Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176 Up to approximately 57 days Terminal phase elimination rate constant (β)
Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176 Minimum first cycle of dosing (up to 21 days) MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity.
Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR) Up to approximately 2 years ORR is defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Dose Escalation Cohort: AUCt for ABBV-176 Up to approximately 57 days Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176.
Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176 Minimum first cycle of dosing (up to 21 days) The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort.
Dose Escalation Cohort: Cmax of ABBV-176 Up to approximately 57 days Maximum observed plasma concentration (Cmax) of ABBV-176.
Dose Escalation Cohort: t1/2 for ABBV-176 Up to approximately 57 days Terminal elimination half-life (t1/2)
- Secondary Outcome Measures
Name Time Method Expanded RPTD Cohort: Overall Survival (OS) Up to 2 years after the last dose of study drug OS is defined as number of days from the date of the first dose to the date of death for all dosed subjects. For subjects who are not deceased, the data will be censored at the date of the last study visit, or the last know date to be alive, whichever is later.
Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176 Up to approximately 15 days Terminal phase elimination rate constant (β) for ABBV-176
Expanded RPTD Cohort: AUCt for ABBV-176 Up to approximately 15 days Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt)
Expanded RPTD Cohort: Tmax of ABBV-176 Up to approximately 15 days Time to Cmax (Tmax) of ABBV-176
Expanded RPTD Cohort: Cmax of ABBV-176 Up to approximately 15 days Maximum observed plasma concentration (Cmax) of ABBV-176.
Expanded RPTD Cohort: Duration of Response (DOR) Up to approximately 2 years DOR is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first.
Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS) Up to approximately 2 years PFS is defined as the time from the participant's first dose of study drug (Day 1) to the date of documented disease progression (per RECIST 1.1), or death due to any cause, whichever occurs first.
Expanded RPTD Cohort: Change in ECOG Performance Status Up to approximately 2 years Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Expanded RPTD Cohort: AUC∞ for ABBV-176 Up to approximately 15 days Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC∞)
Expanded RPTD Cohort: t1/2 for ABBV-176 Up to approximately 15 days Terminal elimination half-life (t1/2) for ABBV-176
Dose Escalation Cohort: Change from Baseline in QTcF Up to approximately 47 days QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline
Trial Locations
- Locations (11)
City of Hope /ID# 161079
🇺🇸Duarte, California, United States
Yale University /ID# 201357
🇺🇸New Haven, Connecticut, United States
St. Lukes Cancer Institute /ID# 201353
🇺🇸Kansas City, Missouri, United States
Washington University-School of Medicine /ID# 162745
🇺🇸Saint Louis, Missouri, United States
Rutgers Cancer Institute of NJ /ID# 161080
🇺🇸New Brunswick, New Jersey, United States
University of Utah /ID# 161606
🇺🇸Salt Lake City, Utah, United States
Sydney Children's Hospital /ID# 162917
🇦🇺Randwick, New South Wales, Australia
Mater Misericordiae /ID# 162918
🇦🇺South Brisbane, Queensland, Australia
Hosp Univ Madrid Sanchinarro /ID# 161644
🇪🇸Madrid, Spain
Rigshospitalet /ID# 159707
🇩🇰Copenhagen Ø, Hovedstaden, Denmark
HonorHealth Research Institute - Pima /ID# 161078
🇺🇸Scottsdale, Arizona, United States