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)

Advanced Solid Tumors Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03145909
• Other study ID #: M15-916
• Secondary ID: 2016-004597-18
• Status: Terminated
• Phase: Phase 1
• Start date: July 3, 2017
• Est. completion date: November 27, 2018

Study information

• Verified date: November 2018
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: November 27, 2018
• Est. primary completion date: November 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer

Intervention

Drug:
• ABBV-176
Intravenous infusion

Locations

Country	Name	City	State
Australia	Sydney Children's Hospital /ID# 162917	Randwick	New South Wales
Australia	Mater Misericordiae /ID# 162918	South Brisbane	Queensland
Denmark	Rigshospitalet /ID# 159707	Copenhagen Ø	Hovedstaden
Spain	Hosp Univ Madrid Sanchinarro /ID# 161644	Madrid
United States	City of Hope /ID# 161079	Duarte	California
United States	St. Lukes Cancer Institute /ID# 201353	Kansas City	Missouri
United States	Rutgers Cancer Institute of NJ /ID# 161080	New Brunswick	New Jersey
United States	Yale University /ID# 201357	New Haven	Connecticut
United States	Washington University-School of Medicine /ID# 162745	Saint Louis	Missouri
United States	University of Utah /ID# 161606	Salt Lake City	Utah
United States	HonorHealth Research Institute - Pima /ID# 161078	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation Cohort: Tmax of ABBV-176	Time to Cmax (Tmax) of ABBV-176	Up to approximately 57 days
Primary	Dose Escalation Cohort: AUC8 for ABBV-176	AUC8 is the area under the plasma concentration-time curve from Time 0 to infinite time.	Up to approximately 57 days
Primary	Dose Escalation Cohort: Terminal phase elimination rate constant (ß) for ABBV-176	Terminal phase elimination rate constant (ß)	Up to approximately 57 days
Primary	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)
Primary	Dose Escalation Cohort: Cmax of ABBV-176	Maximum observed plasma concentration (Cmax) of ABBV-176.	Up to approximately 57 days
Primary	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)
Primary	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
Primary	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
Primary	Dose Escalation Cohort: t1/2 for ABBV-176	Terminal elimination half-life (t1/2)	Up to approximately 57 days
Secondary	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
Secondary	Expanded RPTD Cohort: Tmax of ABBV-176	Time to Cmax (Tmax) of ABBV-176	Up to approximately 15 days
Secondary	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
Secondary	Expanded RPTD Cohort: Cmax of ABBV-176	Maximum observed plasma concentration (Cmax) of ABBV-176.	Up to approximately 15 days
Secondary	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
Secondary	Expanded RPTD Cohort: Terminal phase elimination rate constant (ß) for ABBV-176	Terminal phase elimination rate constant (ß) for ABBV-176	Up to approximately 15 days
Secondary	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
Secondary	Expanded RPTD Cohort: Change in ECOG Performance Status	Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status	Up to approximately 2 years
Secondary	Expanded RPTD Cohort: AUC8 for ABBV-176	Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC8)	Up to approximately 15 days
Secondary	Expanded RPTD Cohort: t1/2 for ABBV-176	Terminal elimination half-life (t1/2) for ABBV-176	Up to approximately 15 days
Secondary	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