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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)

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ClinicalTrials.gov Identifier: NCT03145909
Recruitment Status : Terminated (Safety)
First Posted : May 9, 2017
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Cancer Drug: ABBV-176 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 3, 2017
Actual Primary Completion Date : November 27, 2018
Actual Study Completion Date : November 27, 2018


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




Primary Outcome Measures :
  1. Dose Escalation Cohort: Tmax of ABBV-176 [ Time Frame: Up to approximately 57 days ]
    Time to Cmax (Tmax) of ABBV-176

  2. Dose Escalation Cohort: AUC∞ for ABBV-176 [ Time Frame: Up to approximately 57 days ]
    AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.

  3. Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176 [ Time Frame: Up to approximately 57 days ]
    Terminal phase elimination rate constant (β)

  4. Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176 [ Time Frame: Minimum first cycle of dosing (up to 21 days) ]
    The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort.

  5. Dose Escalation Cohort: Cmax of ABBV-176 [ Time Frame: Up to approximately 57 days ]
    Maximum observed plasma concentration (Cmax) of ABBV-176.

  6. Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176 [ Time Frame: Minimum first cycle of dosing (up to 21 days) ]
    MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity.

  7. Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
    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.

  8. Dose Escalation Cohort: AUCt for ABBV-176 [ Time Frame: Up to approximately 57 days ]
    Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176.

  9. Dose Escalation Cohort: t1/2 for ABBV-176 [ Time Frame: Up to approximately 57 days ]
    Terminal elimination half-life (t1/2)


Secondary Outcome Measures :
  1. Expanded RPTD Cohort: AUCt for ABBV-176 [ Time Frame: Up to approximately 15 days ]
    Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt)

  2. Expanded RPTD Cohort: Tmax of ABBV-176 [ Time Frame: Up to approximately 15 days ]
    Time to Cmax (Tmax) of ABBV-176

  3. Expanded RPTD Cohort: Overall Survival (OS) [ Time Frame: Up to 2 years after the last dose of study drug ]
    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.

  4. Expanded RPTD Cohort: Cmax of ABBV-176 [ Time Frame: Up to approximately 15 days ]
    Maximum observed plasma concentration (Cmax) of ABBV-176.

  5. Expanded RPTD Cohort: Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    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.

  6. Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176 [ Time Frame: Up to approximately 15 days ]
    Terminal phase elimination rate constant (β) for ABBV-176

  7. Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    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.

  8. Expanded RPTD Cohort: Change in ECOG Performance Status [ Time Frame: Up to approximately 2 years ]
    Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

  9. Expanded RPTD Cohort: AUC∞ for ABBV-176 [ Time Frame: Up to approximately 15 days ]
    Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC∞)

  10. Expanded RPTD Cohort: t1/2 for ABBV-176 [ Time Frame: Up to approximately 15 days ]
    Terminal elimination half-life (t1/2) for ABBV-176

  11. Dose Escalation Cohort: Change from Baseline in QTcF [ Time Frame: Up to approximately 47 days ]
    QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03145909


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

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03145909     History of Changes
Other Study ID Numbers: M15-916
2016-004597-18 ( EudraCT Number )
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by AbbVie:
Cancer
Metastatic
Prolactin Receptor (PRLR)
Breast cancer
Colorectal cancer
Adrenocortical carcinoma,
Chromophobe renal cell carcinoma
Hepatocellular carcinoma
Additional relevant MeSH terms:
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Neoplasms