A Study of ABT-414 in Subjects With Solid Tumors

A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Subjects With Advanced Solid Tumors Likely to Over-Express the Epidermal Growth Factor Receptor (EGFR)

A study of ABT-414 in subjects with solid tumors.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Tumors
• Intervention / Treatment: Drug: ABT-414

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ottawa, Canada, K1H 8L6
    • Site Reference ID/Investigator# 89035
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Site Reference ID/Investigator# 90333
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Site Reference ID/Investigator# 83156
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Site Reference ID/Investigator# 117516
    • Boston, Massachusetts, United States, 02215
      • Site Reference ID/Investigator# 83154
  • Texas
    • San Antonio, Texas, United States, 78229
      • Site Reference ID/Investigator# 83155

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:

1. Subjects must have a solid tumor type likely to over-express Epidermal Growth Factor Receptor (EGFR) (Phase 1)
2. Subjects have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
3. Subjects have available tumor tissue
4. Subjects have adequate bone marrow, renal, and hepatic function as follows: Bone marrow: Absolute neutrophil count (ANC) >/= 1,500/mm3 Platelets >/= 100,000/mm3; Hemoglobin >/= 9.0 g/dL Renal function: Serum creatinine </= 1.5 times the upper limit of the institution's normal range Hepatic function: Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) </= 1.5 times the upper limit of the institution's normal range. Subjects with liver metastasis may have an AST and ALT of </= 5.0 x the upper limit of normal.
5. Subjects in the Phase 2 portion must have squamous cell Non-Small Cell Lung Cancer (NSCLC)
6. Eligibility is restricted to subjects with confirmed EGFR amplification in the EGFR amplified cohort

Exclusion Criteria:

1. The subject has uncontrolled metastases to the central nervous system (CNS). Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease for at least 28 days after definitive therapy and have not received prior whole brain radiation (Phase 1 only).
2. The subject has received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy within a period of 28 days prior to the first dose of ABT-414.
3. The subject has unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher.
4. The subject had had major surgery within 28 days prior to the first dose of ABT-414.
5. The subject has a history of immunologic reaction to any Immunoglobulin G (IgG) containing agent.
6. Phase 2 portion only: The subject has previous or concurrent cancer that is distinct in primary site or histology from NSCLC, except cervical carcinoma in situ, non-melanoma carcinoma of the skin or in situ carcinoma of the bladder. Any cancer curatively treated greater than 3 years prior to entry is permitted.

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: ABT-414; Subjects with solid tumors (Phase 1) and squamous non-small cell lung cancer (NSCLC) (Phase 2)	Drug: ABT-414; ABT-414 will be administered by intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 - Safety (Number of subjects with adverse events and/or dose limiting toxicities)	Evaluation of vital signs, clinical lab testing, adverse event monitoring, physical exam and electrocardiogram (ECG) (periodic) under different dosing schedules, drug infusion times, and manufacturing processes.	Every 1-3 weeks for an average of 20 weeks
Phase 1 - Pharmacokinetic profile	Cmax, Cmin, and half-life	Multiple timepoints Week 1 and Week 7
Phase 2 - Efficacy	Objective response per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST)	Every 6-9 weeks for an average of 20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2- Safety (Scheduled study visits occurring on average every 3 weeks)	Evaluation of vital signs, clinical lab testing, and adverse event monitoring, physical exam, and electrocardiogram (periodic)	Followed on average every 3 weeks for approximately 20 weeks
Phase 2- Pharmacokinetic profile	Cmax, Cmin, and half-life	Multiple timepoints Week 1
Phase 1&2 - QT assessment	Triplicate electrocardiograms	Week 1

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Investigators: Study Director: Christopher Ocampo, MD, AbbVie

Publications and helpful links

General Publications

• Munasinghe WP, Mittapalli RK, Li H, Hoffman DM, Holen KD, Menon RM, Xiong H. Evaluation of the effect of the EGFR antibody-drug conjugate ABT-414 on QT interval prolongation in patients with advanced solid tumors likely to over-express EGFR. Cancer Chemother Pharmacol. 2017 May;79(5):915-922. doi: 10.1007/s00280-017-3284-y. Epub 2017 Mar 27.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: September 19, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2017
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell
• Other Study ID Numbers: M13-379