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

Study Overview
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Brief Summary
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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).

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

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

Intervention / Treatment
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* Drug: ABBV-221


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, Cancer, Solid Tumor types likely to exhibit elevated levels of Epidermal Growth Factor Receptor, Solid Tumors