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

Sponsor

AbbVie (Industry)

Overall Status

Terminated

CT.gov ID

NCT02365662

Collaborator

(none)

Enrollment

Locations

Arm

38.1

Actual Duration (Months)

9.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Carcinoma Non-small Cell Lung Cancer Triple Negative Breast Cancer Colorectal Carcinoma Glioblastoma Multiforme	Drug: ABBV-221	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 9, 2015

Actual Primary Completion Date :

Mar 15, 2018

Actual Study Completion Date :

Mar 15, 2018

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	South Texas Accelerated Research Therapeutics	San Antonio	Texas	United States	78229
4	Fundacion Jimenez Diaz	Madrid		Spain	28040
5	Hosp Univ Madrid Sanchinarro	Madrid		Spain	28050