A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)

A Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)

This is an open-label, Phase 1, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-321 for participants with advanced solid tumors likely to overexpress the epidermal growth factor receptor (EGFR). The study will consist of 2 phases: Dose Escalation Phase and Expansion Phase.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors Cancer
• Intervention / Treatment: Drug: ABBV-321

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Northern Cancer Institute /ID# 166138
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health /ID# 217435
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital /ID# 166137
• Israel
  • Ramat Gan, Israel, 5239424
    • Sheba Medical Center /ID# 166398
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group /ID# 166132
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Researc /ID# 166133
    • Sacramento, California, United States, 95817
      • University of California, Davis Comprehensive Cancer Center /ID# 215012
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern University Feinberg School of Medicine /ID# 165191
    • Chicago, Illinois, United States, 60637
      • University of Chicago /ID# 166064
    • Skokie, Illinois, United States, 60077
      • Northshore University Health System Dermatology Clinical Trials Unit /ID# 201095
  • Kentucky
    • Lexington, Kentucky, United States, 40536-7001
      • University of Kentucky Markey Cancer Center /ID# 217665
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute /ID# 212920
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University-School of Medicine /ID# 214955
  • New York
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 167184
    • Stony Brook, New York, United States, 11794-8183
      • Stony Brook University Hospital /ID# 216976
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke University Medical Center /ID# 166135
  • Rhode Island
    • Providence, Rhode Island, United States, 02903-4923
      • Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics /ID# 166134

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Histologically or cytologically confirmed solid tumor of one of the following types associated with overexpression of Epidermal Growth Factor Receptor (EGFR). (For Expansion Phase: Subjects must have EGFR overexpression demonstrated by central assessment or Sponsor selected test).

Dose Escalation Phase:

• Colorectal cancer (CRC), Glioblastoma (GBM), squamous cell carcinoma of the head and neck (HNSCC), non-small cell lung cancer (NSCLC), bladder, cervical, esophageal, kidney or sarcoma.
• Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent. Participants must not be eligible for, or has refused further therapy that is likely to provide a survival benefit.
• Must have measureable disease as per RECIST Version 1.1 or RANO (for GBM).
• Minimum life expectancy of at least 12 weeks.

Expansion Phase (Solid Tumor Cohort):

• Histologically or cytologically confirmed advanced solid tumor.
• Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent.
• Must have measureable disease as per RECIST Version 1.1.
• Minimum life expectancy of at least 12 weeks.

Expansion Phase (GBM Cohort Only):

• Participant has recurrent primary (de novo) glioblastoma histologically confirmed at any time from initial diagnosis through latest recurrence.
• Participant has recurrent GBM per Response Evaluation in Neuro-Oncology (RANO) requirements.
• Tumor is measurable according to RANO criteria.

Exclusion Criteria:

• Active uncontrolled infection National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Grade greater than or equal to 3).
• New York Heart Association (NYHA) Class III or IV heart failure and/or ejection fraction of < 40% as measured by echocardiogram at screening.
• Unstable angina pectoris or cardiac ventricular arrhythmia.
• Myocardial infarction or cerebrovascular accident (CVA) within 6 months.
• Documented history of capillary leak syndrome within 6 months of study enrollment.
• Grade 2 or higher peripheral edema, ascites, pleural, or pericardial effusion within 4 weeks of study enrollment or any history of recurrent grade 2 or higher effusions requiring ongoing drainage.
• Active keratitis or current corneal disorder.
• Laser-assisted in situ keratomileusis (LASIK) procedure within the last 1 year or cataract surgery within the last 3 months.
• Major surgery (including opening of the abdomen, chest) within 21 days of the first dose of study drug.
• Uncontrolled metastases from an extracranial solid tumor to the central nervous system (CNS). Participants with brain metastases from an extracranial solid tumor are eligible after definitive therapy provided they are asymptomatic for at least 2 weeks prior to first dose of ABBV-321.
• No history of medical condition resulting in nephrotic range proteinuria.
• Participants must not have been treated in anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal therapy, biologic therapy or investigational anti-cancer therapy within a period of 21 days or herbal anticancer therapy within 7 days prior to the first dose of study drug.
• For approved targeted small molecules, a washout period of 5 half-lives is adequate (no washout period required for subjects currently on erlotinib)
• Participant must not have been in more than three lines of systemic cytotoxic therapy (excluding adjuvant and neoadjuvant therapy)

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: ABBV-321; ABBV-321 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.	Drug: ABBV-321; Intravenous infusion; Other Names: Serclutamab Talirine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCt for ABBV-321	Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321	Up to 78 days post dose
AUC∞ for ABBV-321	AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.	Up to 78 days post dose
Tmax of ABBV-321	Time to Cmax (Tmax) of ABBV-321	Up to 78 days post dose
Terminal phase elimination rate constant (β) for ABBV-321	Terminal phase elimination rate constant (β)	Up to 78 days post dose
Cmax of ABBV-321	Maximum observed plasma concentration (Cmax) of ABBV-321	Up to 78 days post dose
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321	The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Phase	Minimum first cycle of dosing (up to 28 days)
t1/2 for ABBV-321	Terminal elimination half-life (t1/2)	Up to 78 days post dose
Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321	The MTD of ABBV-321 will be determined during the dose escalation phase of the study.	Minimum first cycle of dosing (up to 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.	Up to approximately 5 years
Duration of Response (DOR)	DOR for a given participant is defined as the number of days from the day CR or PR (whichever is recorded first) occurred to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.	Up to approximately 5 years
Disease Control Rate (DCR)	DCR is defined as the proportion of participants with objective evidence of complete response (CR), partial response (PR) or stable disease (SD); a participants best overall response assignment of SD must be maintained for at least 6 weeks since the first dose date of study drug.	Up to 5 years
Time to progression (TTP)	TTP is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST version 1.1 or RANO criteria.	Up to approximately 5 years
Change from Baseline in QTcF	QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline	Up to 61 days post dose
Overall Survival (OS)	OS is defined as number of days from the date of the first dose to the date of death for all dosed participants. For participants who are not deceased, the data will be censored at the last known date to be alive.	Up to approximately 5 years
Objective response rate (ORR)	ORR is defined as the proportion of participants with a response of partial response (PR) or better; Response Assessment in Neuro-Oncology (RANO) criteria will be used for glioblastoma (GBM) participants, and Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria will be used for all other participants.	Up to 5 years

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Actual): April 14, 2021
• Study Completion (Actual): April 14, 2021

Study Registration Dates

• First Submitted: July 27, 2017
• First Submitted That Met QC Criteria: July 27, 2017
• First Posted (Actual): July 31, 2017

Study Record Updates

• Last Update Posted (Actual): May 6, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Cancer; Advanced Solid Tumors; non-small cell lung cancer (NSCLC); Epidermal Growth Factor Receptor (EGFR); Glioblastoma (GBM); Squamous cell carcinoma of the head and neck (HNSCC); overexpression of Epidermal Growth Factor Receptor (EGFR)
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: M16-438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No