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

A Phase 1 Study of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor

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).

Study Overview

• Status: Terminated
• Conditions: Glioblastoma Multiforme; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Colorectal Carcinoma
• Intervention / Treatment: Drug: ABBV-221

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz
  • Madrid, Spain, 28050
    • Hosp Univ Madrid Sanchinarro
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor	Drug: ABBV-221; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effect of systemic ABBV-221 administration on QT prolongation	ECG parameters will be descriptively summarized, and the relationship between change of baseline of QT interval corrected for heart rate and concentration of three analytes will be explored.	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)	ORR is the proportion of participants with objective response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (complete or partial objective response) will be calculated for all dosed participants with at least one measurable lesion at baseline.	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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2015
• Primary Completion (Actual): March 15, 2018
• Study Completion (Actual): March 15, 2018

Study Registration Dates

• First Submitted: February 5, 2015
• First Submitted That Met QC Criteria: February 16, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2018
• Last Update Submitted That Met QC Criteria: March 28, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Oncology; Solid Tumors; Solid Tumor types likely to exhibit elevated levels of Epidermal Growth Factor Receptor
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Head and Neck Neoplasms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma, Squamous Cell; Breast Neoplasms; Carcinoma; Glioblastoma; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms
• Other Study ID Numbers: M14-429; 2014-003557-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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