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)

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors Cancer
• Intervention / Treatment: Drug: ABBV-176

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohort; ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached.	Drug: ABBV-176; Intravenous infusion
Experimental: 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	Drug: ABBV-176; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Cohort: Tmax of ABBV-176	Time to Cmax (Tmax) of ABBV-176	Up to approximately 57 days
Dose Escalation Cohort: AUC∞ for ABBV-176	AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.	Up to approximately 57 days
Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176	Terminal phase elimination rate constant (β)	Up to approximately 57 days
Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176	The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort.	Minimum first cycle of dosing (up to 21 days)
Dose Escalation Cohort: Cmax of ABBV-176	Maximum observed plasma concentration (Cmax) of ABBV-176.	Up to approximately 57 days
Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176	MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity.	Minimum first cycle of dosing (up to 21 days)
Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR)	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.	Up to approximately 2 years
Dose Escalation Cohort: AUCt for ABBV-176	Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176.	Up to approximately 57 days
Dose Escalation Cohort: t1/2 for ABBV-176	Terminal elimination half-life (t1/2)	Up to approximately 57 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded RPTD Cohort: AUCt for ABBV-176	Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt)	Up to approximately 15 days
Expanded RPTD Cohort: Tmax of ABBV-176	Time to Cmax (Tmax) of ABBV-176	Up to approximately 15 days
Expanded RPTD Cohort: Overall Survival (OS)	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.	Up to 2 years after the last dose of study drug
Expanded RPTD Cohort: Cmax of ABBV-176	Maximum observed plasma concentration (Cmax) of ABBV-176.	Up to approximately 15 days
Expanded RPTD Cohort: Duration of Response (DOR)	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.	Up to approximately 2 years
Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176	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)	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.	Up to approximately 2 years
Expanded RPTD Cohort: Change in ECOG Performance Status	Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status	Up to approximately 2 years
Expanded RPTD Cohort: AUC∞ for ABBV-176	Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC∞)	Up to approximately 15 days
Expanded RPTD Cohort: t1/2 for ABBV-176	Terminal elimination half-life (t1/2) for ABBV-176	Up to approximately 15 days
Dose Escalation Cohort: Change from Baseline in QTcF	QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline	Up to approximately 47 days

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2017
• Primary Completion (Actual): November 27, 2018
• Study Completion (Actual): November 27, 2018

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): November 29, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Colorectal cancer; Breast cancer; Metastatic; Hepatocellular carcinoma; Prolactin Receptor (PRLR); Adrenocortical carcinoma,; Chromophobe renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: M15-916; 2016-004597-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No