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)

NCT03234712 | Completed Phase 1 FDA Drug

• 1 other identifier: M16-438
• Study Type: interventional
• Target: 62
• Locations: 3 countries
• Sites: 18

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.

Conditions

Advanced Solid Tumors Cancer

Keywords

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)

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (7)

• Progression-Free Survival (PFS)

  Up to approximately 5 years

• Duration of Response (DOR)

  Up to approximately 5 years

• Disease Control Rate (DCR)

  Up to 5 years

• Time to progression (TTP)

  Up to approximately 5 years

• Change from Baseline in QTcF

  Up to 61 days post dose

Study Arms (1)

ABBV-321

EXPERIMENTAL

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

Interventions

ABBV-321 DRUG

Intravenous infusion

Also known as: Serclutamab Talirine

ABBV-321

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• AbbVie: lead

Study Sites (18)

Highlands Oncology Group /ID# 166132

Springdale, Arkansas, 72762, United States

Location

The Angeles Clinic and Researc /ID# 166133

Los Angeles, California, 90025, United States

Location

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

Sacramento, California, 95817, United States

Location

Northwestern University Feinberg School of Medicine /ID# 165191

Chicago, Illinois, 60611-2927, United States

Location

University of Chicago /ID# 166064

Chicago, Illinois, 60637, United States

Location

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

Skokie, Illinois, 60077, United States

Location

University of Kentucky Markey Cancer Center /ID# 217665

Lexington, Kentucky, 40536-7001, United States

Location

Dana-Farber Cancer Institute /ID# 212920

Boston, Massachusetts, 02215, United States

Location

Washington University-School of Medicine /ID# 214955

St Louis, Missouri, 63110, United States

Location

Columbia Univ Medical Center /ID# 167184

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

Location

Stony Brook University Hospital /ID# 216976

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

Location

Duke University Medical Center /ID# 166135

Durham, North Carolina, 27710-3000, United States

Location

Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600

Providence, Rhode Island, 02903-4923, United States

Location

South Texas Accelerated Research Therapeutics /ID# 166134

San Antonio, Texas, 78229, United States

Location

Northern Cancer Institute /ID# 166138

St Leonards, New South Wales, 2065, Australia

Location

Monash Health /ID# 217435

Clayton, Victoria, 3168, Australia

Location

Austin Hospital /ID# 166137

Heidelberg, Victoria, 3084, Australia

Location

Sheba Medical Center /ID# 166398

Ramat Gan, 5239424, Israel

Location

Related Publications (1)

• Carneiro BA, Papadopoulos KP, Strickler JH, Lassman AB, Waqar SN, Chae YK, Patel JD, Shacham-Shmueli E, Kelly K, Khasraw M, Bestvina CM, Merrell R, Huang K, Atluri H, Ansell P, Li R, Jin J, Anderson MG, Reilly EB, Morrison-Thiele G, Patel K, Robinson RR, Aristide MRN, Gan HK. Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma. Neurooncol Adv. 2022 Dec 21;5(1):vdac183. doi: 10.1093/noajnl/vdac183. eCollection 2023 Jan-Dec.

  PMID: 36814898 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Glioblastoma; Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: July 31, 2017
• Study Start: October 10, 2017
• Primary Completion: April 14, 2021
• Study Completion: April 14, 2021
• Last Updated: May 6, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); AU (3); IL (1)