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

Phase 1

Terminated

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

• Registration Number: NCT02365662
• Lead Sponsor: AbbVie

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-09
• Study First Submitted: 2015-02-05
• Study First Submitted QC: 2015-02-16
• Study First Posted: 2015-02-19
• Status Verified: 2018-03
• Primary Completion: 2018-03-15
• Study Completion: 2018-03-15
• Last Update Submitted: 2018-03-28
• Last Update Posted: 2018-03-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	ABBV-221	Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of ABBV-221	Up to 2 years from first dose of study drug.	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.
Area Under the Plasma Concentration-time Curve of ABBV-221	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).	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.
Number of participants with adverse events	Measured for approximately 4 years	Adverse event monitoring will be performed during the study
Maximum Plasma Concentration (Cmax) of ABBV-221	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).	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.
Recommended Phase 2 dose of ABBV-221	1 day of study drug administration within the 21-day cycle at the designated cohort dose	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.
Area Under the Plasma Concentration-time Curve from 0 to the Time of the Last Measurable Concentration (AUCt) of ABBV-221	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).	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.

Secondary Outcome Measures

Name	Time	Method
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)	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.
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	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.

Trial Locations

Locations (5)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hosp Univ Madrid Sanchinarro; 🇪🇸 Madrid, Spain

South Texas Accelerated Research Therapeutics; 🇺🇸 San Antonio, Texas, United States