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)

A Phase 1 Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)

Sponsors

Lead Sponsor: AbbVie

Source 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.

Overall Status Terminated
Start Date July 3, 2017
Completion Date November 27, 2018
Primary Completion Date November 27, 2018
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Dose Escalation Cohort: Tmax of ABBV-176 Up to approximately 57 days
Dose Escalation Cohort: AUC∞ for ABBV-176 Up to approximately 57 days
Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176 Up to approximately 57 days
Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176 Minimum first cycle of dosing (up to 21 days)
Dose Escalation Cohort: Cmax of ABBV-176 Up to approximately 57 days
Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176 Minimum first cycle of dosing (up to 21 days)
Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR) Up to approximately 2 years
Dose Escalation Cohort: AUCt for ABBV-176 Up to approximately 57 days
Dose Escalation Cohort: t1/2 for ABBV-176 Up to approximately 57 days
Secondary Outcome
Measure Time Frame
Expanded RPTD Cohort: AUCt for ABBV-176 Up to approximately 15 days
Expanded RPTD Cohort: Tmax of ABBV-176 Up to approximately 15 days
Expanded RPTD Cohort: Overall Survival (OS) Up to 2 years after the last dose of study drug
Expanded RPTD Cohort: Cmax of ABBV-176 Up to approximately 15 days
Expanded RPTD Cohort: Duration of Response (DOR) Up to approximately 2 years
Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176 Up to approximately 15 days
Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS) Up to approximately 2 years
Expanded RPTD Cohort: Change in ECOG Performance Status Up to approximately 2 years
Expanded RPTD Cohort: AUC∞ for ABBV-176 Up to approximately 15 days
Expanded RPTD Cohort: t1/2 for ABBV-176 Up to approximately 15 days
Dose Escalation Cohort: Change from Baseline in QTcF Up to approximately 47 days
Enrollment 19
Condition
Intervention

Intervention Type: Drug

Intervention Name: ABBV-176

Description: Intravenous infusion

Eligibility

Criteria:

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- Participant has prior exposure to any pyrrolobenzodiazopine-containing agent

- Participant has unresolved, clinically significant toxicities from prior anticancer therapy, defined as greater than Grade 1 on Common Terminology for adverse events.

- Participant has clinically significant uncontrolled conditions.

- Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG).

- 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.

- Participant has a history of >= grade 3 AST, ALT, or bilirubin increase or has extensive liver resection (i.e., left lobe resection).

- Participant has a history of cholecystitis (subject with history of cholecystectomy will not be excluded), or has active gallbladder disease.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
AbbVie Inc. Study Director AbbVie
Location
Facility:
HonorHealth Research Institute - Pima /ID# 161078 | Scottsdale, Arizona, 85258-2345, United States
City of Hope /ID# 161079 | Duarte, California, 91010, United States
Yale University /ID# 201357 | New Haven, Connecticut, 06510, United States
St. Lukes Cancer Institute /ID# 201353 | Kansas City, Missouri, 64111-5905, United States
Washington University-School of Medicine /ID# 162745 | Saint Louis, Missouri, 63110, United States
Rutgers Cancer Institute of NJ /ID# 161080 | New Brunswick, New Jersey, 08903, United States
University of Utah /ID# 161606 | Salt Lake City, Utah, 84112-5500, United States
Sydney Children's Hospital /ID# 162917 | Randwick, New South Wales, 2031, Australia
Mater Misericordiae /ID# 162918 | South Brisbane, Queensland, 4101, Australia
Rigshospitalet /ID# 159707 | Copenhagen Ø, Hovedstaden, 2100, Denmark
Hosp Univ Madrid Sanchinarro /ID# 161644 | Madrid, 28050, Spain
Location Countries

Australia

Denmark

Spain

United States

Verification Date

November 2018

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Dose Escalation Cohort

Type: Experimental

Description: ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached.

Label: Expanded RPTD Cohort

Type: Experimental

Description: ABBV-176 via intravenous administration in participants with breast cancer at the Recommended Phase Two Dose (RPTD) determined during the Dose Escalation Cohort

Patient Data Undecided
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov