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)

• ClinicalTrials.gov Identifier: NCT03234712
• Recruitment Status: Completed
• First Posted: July 31, 2017
• Last Update Posted: May 6, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors Cancer	Drug: ABBV-321	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: October 10, 2017
• Actual Primary Completion Date: April 14, 2021
• Actual Study Completion Date: April 14, 2021

Arms and Interventions

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 Name: Serclutamab Talirine

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
   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.
2. Duration of Response (DOR) [ Time Frame: Up to approximately 5 years ]
   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.
3. Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
   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.
4. Time to progression (TTP) [ Time Frame: Up to approximately 5 years ]
   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.
5. Change from Baseline in QTcF [ Time Frame: Up to 61 days post dose ]
   QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline
6. Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
   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.
7. Objective response rate (ORR) [ Time Frame: Up to 5 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Arkansas

Highlands Oncology Group /ID# 166132

Springdale, Arkansas, United States, 72762

United States, California

The Angeles Clinic and Researc /ID# 166133

Los Angeles, California, United States, 90025

University of California, Davis Comprehensive Cancer Center /ID# 215012

Sacramento, California, United States, 95817

United States, Illinois

Northwestern University Feinberg School of Medicine /ID# 165191

Chicago, Illinois, United States, 60611-2927

University of Chicago /ID# 166064

Chicago, Illinois, United States, 60637

Northshore University Health System Dermatology Clinical Trials Unit /ID# 201095

Skokie, Illinois, United States, 60077

United States, Kentucky

University of Kentucky Markey Cancer Center /ID# 217665

Lexington, Kentucky, United States, 40536-7001

United States, Massachusetts

Dana-Farber Cancer Institute /ID# 212920

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University-School of Medicine /ID# 214955

Saint Louis, Missouri, United States, 63110

United States, New York

Columbia Univ Medical Center /ID# 167184

New York, New York, United States, 10032-3725

Stony Brook University Hospital /ID# 216976

Stony Brook, New York, United States, 11794-8183

United States, North Carolina

Duke University Medical Center /ID# 166135

Durham, North Carolina, United States, 27710-3000

United States, Rhode Island

Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600

Providence, Rhode Island, United States, 02903-4923

United States, Texas

South Texas Accelerated Research Therapeutics /ID# 166134

San Antonio, Texas, United States, 78229

Australia, New South Wales

Northern Cancer Institute /ID# 166138

St Leonards, New South Wales, Australia, 2065

Australia, Victoria

Monash Health /ID# 217435

Clayton, Victoria, Australia, 3168

Austin Hospital /ID# 166137

Heidelberg, Victoria, Australia, 3084

Israel

Sheba Medical Center /ID# 166398

Ramat Gan, Israel, 5239424

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: ABBVIE INC.; AbbVie

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03234712
• Other Study ID Numbers: M16-438
• First Posted: July 31, 2017
• Last Update Posted: May 6, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by AbbVie:

Advanced Solid Tumors; Epidermal Growth Factor Receptor (EGFR); Squamous cell carcinoma of the head and neck (HNSCC); non-small cell lung cancer (NSCLC); Glioblastoma (GBM); Cancer; overexpression of Epidermal Growth Factor Receptor (EGFR)

Additional relevant MeSH terms:

Neoplasms