Clinical trial NCT03145909: 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)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Cancer
Metastatic
Prolactin Receptor (PRLR)
Breast cancer
Colorectal cancer
Adrenocortical carcinoma,
Chromophobe renal cell carcinoma
Hepatocellular carcinoma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-05-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Dose Escalation Cohort: Tmax of ABBV-176
timeFrame: Up to approximately 57 days
measure: Dose Escalation Cohort: AUC∞ for ABBV-176
timeFrame: Up to approximately 57 days
measure: Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176
timeFrame: Up to approximately 57 days
measure: Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176
timeFrame: Minimum first cycle of dosing (up to 21 days)
measure: Dose Escalation Cohort: Cmax of ABBV-176
timeFrame: Up to approximately 57 days
measure: Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176
timeFrame: Minimum first cycle of dosing (up to 21 days)
measure: Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Dose Escalation Cohort: AUCt for ABBV-176
timeFrame: Up to approximately 57 days
measure: Dose Escalation Cohort: t1/2 for ABBV-176
timeFrame: Up to approximately 57 days
Secondary outcomes:
measure: Expanded RPTD Cohort: AUCt for ABBV-176
timeFrame: Up to approximately 15 days
measure: Expanded RPTD Cohort: Tmax of ABBV-176
timeFrame: Up to approximately 15 days
measure: Expanded RPTD Cohort: Overall Survival (OS)
timeFrame: Up to 2 years after the last dose of study drug
measure: Expanded RPTD Cohort: Cmax of ABBV-176
timeFrame: Up to approximately 15 days
measure: Expanded RPTD Cohort: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176
timeFrame: Up to approximately 15 days
measure: Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Expanded RPTD Cohort: Change in ECOG Performance Status
timeFrame: Up to approximately 2 years
measure: Expanded RPTD Cohort: AUC∞ for ABBV-176
timeFrame: Up to approximately 15 days
measure: Expanded RPTD Cohort: t1/2 for ABBV-176
timeFrame: Up to approximately 15 days
measure: Dose Escalation Cohort: Change from Baseline in QTcF
timeFrame: Up to approximately 47 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Pima /ID# 161078
state: Arizona
city: Duarte
country: United States
facility: City of Hope /ID# 161079
state: California
city: New Haven
country: United States
facility: Yale University /ID# 201357
state: Connecticut
city: Kansas City
country: United States
facility: St. Lukes Cancer Institute /ID# 201353
state: Missouri
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 162745
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of NJ /ID# 161080
state: New Jersey
city: Salt Lake City
country: United States
facility: University of Utah /ID# 161606
state: Utah
city: Randwick
country: Australia
facility: Sydney Children's Hospital /ID# 162917
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae /ID# 162918
state: Queensland
city: Copenhagen Ø
country: Denmark
facility: Rigshospitalet /ID# 159707
state: Hovedstaden
city: Madrid
country: Spain
facility: Hosp Univ Madrid Sanchinarro /ID# 161644
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.