A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor

NCT02365662 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M14-4292014-003557-34
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 5

Brief Summary

This is an open-label, Phase I, dose escalation study to determine the recommended Phase 2 dose, maximum tolerated dose, and evaluate the safety and pharmacokinetic profile of ABBV-221 in participants with advanced solid tumors likely to exhibit elevated levels of Epidermal Growth Factor Receptor (EGFR).

Conditions

Head and Neck Squamous Cell Carcinoma; Non-small Cell Lung Cancer; Triple Negative Breast Cancer; Colorectal Carcinoma; Glioblastoma Multiforme

Keywords

Oncology; Cancer; Solid Tumor types likely to exhibit elevated levels of Epidermal Growth Factor Receptor; Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Number of participants with adverse events

  Adverse event monitoring will be performed during the study

  Measured for approximately 4 years

• Maximum Plasma Concentration (Cmax) of ABBV-221

  The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the plasma after administration in a dosing interval.

  Blood samples will be collected before infusion (0 hour, pre-dose) on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D5, C1D8, C1D15, C2D1, C3D1, C3D2, C3D3, C3D5, C3D8, C3D15, every 2 cycles starting with Cycle 5, and at the final visit (approximately 2 years).

• Area Under the Plasma Concentration-time Curve from 0 to the Time of the Last Measurable Concentration (AUCt) of ABBV-221

  The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma.

  Blood samples will be collected before infusion (0 hour, pre-dose) on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D5, C1D8, C1D15, C2D1, C3D1, C3D2, C3D3, C3D5, C3D8, C3D15, every 2 cycles starting with Cycle 5, and at the final visit (approximately 2 years).

• Maximum tolerated dose of ABBV-221

  The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.

  Up to 2 years from first dose of study drug.

• Area Under the Plasma Concentration-time Curve of ABBV-221

  The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma.

  Blood samples will be collected before infusion (0 hour, pre-dose) on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D5, C1D8, C1D15, C2D1, C3D1, C3D2, C3D3, C3D5, C3D8, C3D15, every 2 cycles starting with Cycle 5, and at the final visit (approximately 2 years).

• Recommended Phase 2 dose of ABBV-221

  If a maximum tolerated dose (MTD) is reached, the recommended Phase 2 dose (RPTD) of ABBV-221 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and pharmacokinetic data.

  1 day of study drug administration within the 21-day cycle at the designated cohort dose

Secondary Outcomes (2)

• Assess the effect of systemic ABBV-221 administration on QT prolongation

  At Days 1, 2, 3, 5, 8 of Cycle 1; Day 1 of every cycle starting at Cycle 2, and Final Visit (approximately 2 years from first dose of study drug)

• Objective Response Rate (ORR)

  At screening; at the end of Cycle 2 and the end of every 3 cycles for approximately 2 years from first dose of study drug

Study Arms (1)

Arm 1

EXPERIMENTAL

Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor

Drug: ABBV-221

Interventions

ABBV-221 DRUG

ABBV-221 will be given either every 3 weeks or 2 weeks on, 1 week off or weekly dosing by intravenous infusion approximately over 30 minutes to 3 hours. This is a dose escalation study, therefore the dose of ABBV-221 will change throughout the study.

Arm 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 2.
• Has a solid tumor likely to exhibit elevated levels of EGFR (e.g. head and neck squamous cell carcinoma, non-small cell lung cancer, triple negative breast cancer ,colorectal carcinoma and glioblastoma multiforme).
• Has an archived, diagnostic tumor tissue available for analysis.
• Has adequate hematologic, renal, cardiac and hepatic function.
• Expanded Safety Cohort participants must have confirmed metastatic lung cancer and progressed after receiving prior platinum-containing chemotherapy.

You may not qualify if:

• Previously received an EGFR-directed monoclonal antibody within the past 4 weeks.
• Has unresolved, clinically significant toxicities from prior anti-cancer therapy defined as \> Grade 1 on Common Terminology Criteria for Adverse Events.
• History of major immunologic reaction to any IgG containing agent.
• Any medical condition which in the opinion of the investigator places the participant at an unacceptably high risk for toxicities.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hosp Univ Madrid Sanchinarro

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Colorectal Neoplasms; Glioblastoma; Neoplasms

Interventions

depatuxizumab mafodotin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; 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; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 19, 2015
• Study Start: January 9, 2015
• Primary Completion: March 15, 2018
• Study Completion: March 15, 2018
• Last Updated: March 30, 2018

Record last verified: 2018-03

Locations

US (3); ES (2)