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)

NCT03145909 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M15-9162016-004597-18
• Study Type: interventional
• Target: 19
• Locations: 4 countries
• Sites: 11

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.

Conditions

Advanced Solid Tumors Cancer

Keywords

Cancer; Metastatic; Prolactin Receptor (PRLR); Breast cancer; Colorectal cancer; Adrenocortical carcinoma,; Chromophobe renal cell carcinoma; Hepatocellular carcinoma

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (11)

• Expanded RPTD Cohort: AUCt for ABBV-176

  Up to approximately 15 days

• Expanded RPTD Cohort: Tmax of ABBV-176

  Up to approximately 15 days

• Expanded RPTD Cohort: Overall Survival (OS)

  Up to 2 years after the last dose of study drug

• Expanded RPTD Cohort: Cmax of ABBV-176

  Up to approximately 15 days

• Expanded RPTD Cohort: Duration of Response (DOR)

  Up to approximately 2 years

Study Arms (2)

Dose Escalation Cohort

EXPERIMENTAL

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

Drug: ABBV-176

Expanded RPTD Cohort

EXPERIMENTAL

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

Interventions

ABBV-176 DRUG

Intravenous infusion

Dose Escalation Cohort; Expanded RPTD Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (11)

HonorHealth Research Institute - Pima /ID# 161078

Scottsdale, Arizona, 85258-2345, United States

Location

City of Hope /ID# 161079

Duarte, California, 91010, United States

Location

Yale University /ID# 201357

New Haven, Connecticut, 06510, United States

Location

St. Lukes Cancer Institute /ID# 201353

Kansas City, Missouri, 64111-5905, United States

Location

Washington University-School of Medicine /ID# 162745

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of NJ /ID# 161080

New Brunswick, New Jersey, 08903, United States

Location

University of Utah /ID# 161606

Salt Lake City, Utah, 84112-5500, United States

Location

Sydney Children's Hospital /ID# 162917

Randwick, New South Wales, 2031, Australia

Location

Mater Misericordiae /ID# 162918

South Brisbane, Queensland, 4101, Australia

Location

Rigshospitalet /ID# 159707

Copenhagen Ø, Capital Region, 2100, Denmark

Location

Hosp Univ Madrid Sanchinarro /ID# 161644

Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 32524319 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Breast Neoplasms; Colorectal Neoplasms; Adrenocortical Carcinoma; Carcinoma, Renal Cell; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Neoplasms; Liver Diseases

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2017
• First Posted: May 9, 2017
• Study Start: July 3, 2017
• Primary Completion: November 27, 2018
• Study Completion: November 27, 2018
• Last Updated: November 29, 2018

Record last verified: 2018-11

Locations

DK (1); ES (1); US (7); AU (2)