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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02365662
• Other study ID #: M14-429
• Secondary ID: 2014-003557-34
• Status: Terminated
• Phase: Phase 1
• First received: February 5, 2015
• Last updated: March 28, 2018
• Start date: January 9, 2015
• Est. completion date: March 15, 2018

Study information

• Verified date: March 2018
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: March 15, 2018
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Colorectal Carcinoma
• Colorectal Neoplasms
• Glioblastoma
• Glioblastoma Multiforme
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Non-small Cell Lung Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hosp Univ Madrid Sanchinarro	Madrid
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	Adverse event monitoring will be performed during the study	Measured for approximately 4 years
Primary	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).
Primary	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).
Primary	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.
Primary	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).
Primary	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	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)
Secondary	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