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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03234712
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : November 18, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE July 27, 2017
First Posted Date  ICMJE July 31, 2017
Last Update Posted Date November 18, 2019
Actual Study Start Date  ICMJE October 10, 2017
Estimated Primary Completion Date March 7, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
  • 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
  • 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.
  • Tmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Time to Cmax (Tmax) of ABBV-321
  • Terminal phase elimination rate constant (β) for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal phase elimination rate constant (β)
  • Cmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Maximum observed plasma concentration (Cmax) of ABBV-321
  • 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
  • t1/2 for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal elimination half-life (t1/2)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 27, 2017)
  • 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.
  • 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
  • Dose Escalation Phase: Cmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Maximum observed plasma concentration (Cmax) of ABBV-321
  • Dose Escalation Phase: Tmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Time to Cmax (Tmax) of ABBV-321
  • Dose Escalation Phase: Terminal phase elimination rate constant (β) for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal phase elimination rate constant (β)
  • Dose Escalation Phase: t1/2 for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal elimination half-life (t1/2)
  • Dose Escalation Phase: 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
  • Dose Escalation Phase: 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.
  • Expanded Safety Phase: Cmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Maximum observed plasma concentration (Cmax) of ABBV-321
  • Expanded Safety Phase: Tmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Time to Cmax (Tmax) of ABBV-321
  • Expanded Safety Phase: Terminal phase elimination rate constant (β) for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal phase elimination rate constant (β)
  • Expanded Safety Phase: t1/2 for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal elimination half-life (t1/2)
  • Expanded Safety Phase: 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
  • Expanded Safety Phase: 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2017)
  • 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
  • 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.
  • 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.
  • 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.
  • Time to progression (TTP) [ Time Frame: Up to approximately 5 years ]
    TPP 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors Cancer
Intervention  ICMJE Drug: ABBV-321
Intravenous infusion
Other Name: Serclutamab Talirine
Study Arms  ICMJE 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.
Intervention: Drug: ABBV-321
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 25, 2018)
120
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2017)
80
Estimated Study Completion Date  ICMJE September 4, 2025
Estimated Primary Completion Date March 7, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Australia,   Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03234712
Other Study ID Numbers  ICMJE M16-438
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP