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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03145909




Registration number
NCT03145909
Ethics application status
Date submitted
5/05/2017
Date registered
9/05/2017
Date last updated
29/11/2018

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
2016-004597-18
Secondary ID [2] 0 0
M15-916
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-176

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

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


Treatment: Drugs: ABBV-176
Intravenous infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation Cohort: Tmax of ABBV-176 - Time to Cmax (Tmax) of ABBV-176
Timepoint [1] 0 0
Up to approximately 57 days
Primary outcome [2] 0 0
Dose Escalation Cohort: AUC8 for ABBV-176 - AUC8 is the area under the plasma concentration-time curve from Time 0 to infinite time.
Timepoint [2] 0 0
Up to approximately 57 days
Primary outcome [3] 0 0
Dose Escalation Cohort: Terminal phase elimination rate constant (ß) for ABBV-176 - Terminal phase elimination rate constant (ß)
Timepoint [3] 0 0
Up to approximately 57 days
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Minimum first cycle of dosing (up to 21 days)
Primary outcome [5] 0 0
Dose Escalation Cohort: Cmax of ABBV-176 - Maximum observed plasma concentration (Cmax) of ABBV-176.
Timepoint [5] 0 0
Up to approximately 57 days
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
Minimum first cycle of dosing (up to 21 days)
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to approximately 2 years
Primary outcome [8] 0 0
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.
Timepoint [8] 0 0
Up to approximately 57 days
Primary outcome [9] 0 0
Dose Escalation Cohort: t1/2 for ABBV-176 - Terminal elimination half-life (t1/2)
Timepoint [9] 0 0
Up to approximately 57 days
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to approximately 15 days
Secondary outcome [2] 0 0
Expanded RPTD Cohort: Tmax of ABBV-176 - Time to Cmax (Tmax) of ABBV-176
Timepoint [2] 0 0
Up to approximately 15 days
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to 2 years after the last dose of study drug
Secondary outcome [4] 0 0
Expanded RPTD Cohort: Cmax of ABBV-176 - Maximum observed plasma concentration (Cmax) of ABBV-176.
Timepoint [4] 0 0
Up to approximately 15 days
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to approximately 2 years
Secondary outcome [6] 0 0
Expanded RPTD Cohort: Terminal phase elimination rate constant (ß) for ABBV-176 - Terminal phase elimination rate constant (ß) for ABBV-176
Timepoint [6] 0 0
Up to approximately 15 days
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to approximately 2 years
Secondary outcome [8] 0 0
Expanded RPTD Cohort: Change in ECOG Performance Status - Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [8] 0 0
Up to approximately 2 years
Secondary outcome [9] 0 0
Expanded RPTD Cohort: AUC8 for ABBV-176 - Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC8)
Timepoint [9] 0 0
Up to approximately 15 days
Secondary outcome [10] 0 0
Expanded RPTD Cohort: t1/2 for ABBV-176 - Terminal elimination half-life (t1/2) for ABBV-176
Timepoint [10] 0 0
Up to approximately 15 days
Secondary outcome [11] 0 0
Dose Escalation Cohort: Change from Baseline in QTcF - QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline
Timepoint [11] 0 0
Up to approximately 47 days

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Sydney Children's Hospital /ID# 162917 - Randwick
Recruitment hospital [2] 0 0
Mater Misericordiae /ID# 162918 - South Brisbane
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
Denmark
State/province [7] 0 0
Hovedstaden
Country [8] 0 0
Spain
State/province [8] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03145909
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03145909