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)

NCT ID: NCT03145909

Last Updated: 2018-11-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-03
• Study Completion Date: 2018-11-27

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.

Conditions

Advanced Solid Tumors Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation Cohort

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

Group Type: EXPERIMENTAL

ABBV-176

Intervention Type: DRUG

Intravenous infusion

Expanded RPTD Cohort

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

Group Type: EXPERIMENTAL

ABBV-176

Intervention Type: DRUG

Intravenous infusion

Interventions

ABBV-176

Intravenous infusion

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

HonorHealth Research Institute - Pima /ID# 161078

Scottsdale, Arizona, United States

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

St 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

Rigshospitalet /ID# 159707

Copenhagen Ø, Capital Region, Denmark

Hosp Univ Madrid Sanchinarro /ID# 161644

Madrid, , Spain

Countries

United States; Australia; Denmark; Spain

References

Lemech C, Woodward N, Chan N, Mortimer J, Naumovski L, Nuthalapati S, Tong B, Jiang F, Ansell P, Ratajczak CK, Sachdev J. A first-in-human, phase 1, dose-escalation study of ABBV-176, an antibody-drug conjugate targeting the prolactin receptor, in patients with advanced solid tumors. Invest New Drugs. 2020 Dec;38(6):1815-1825. doi: 10.1007/s10637-020-00960-z. Epub 2020 Jun 10.

Reference Type: DERIVED

PMID: 32524319 (View on PubMed)

Other Identifiers

2016-004597-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M15-916

Identifier Type: -

Identifier Source: org_study_id