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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) or Its Ligands

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ClinicalTrials.gov Identifier: NCT03234712
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

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) or its ligands. The study will consist of 2 phases: Dose Escalation Phase and Expanded Safety Phase.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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) or Its Ligands
Actual Study Start Date : October 10, 2017
Estimated Primary Completion Date : September 1, 2019
Estimated Study Completion Date : July 22, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Urogastrone

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




Primary Outcome Measures :
  1. 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

  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

  3. 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.

  4. Dose Escalation Phase: Tmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Time to Cmax (Tmax) of ABBV-321

  5. 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)

  6. Dose Escalation Phase: Cmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Maximum observed plasma concentration (Cmax) of ABBV-321

  7. 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

  8. Dose Escalation Phase: t1/2 for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal elimination half-life (t1/2)

  9. 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)

  10. Expanded Safety Phase: Cmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Maximum observed plasma concentration (Cmax) of ABBV-321

  11. Expanded Safety Phase: t1/2 for ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Terminal elimination half-life (t1/2)

  12. 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.

  13. 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.

  14. Expanded Safety Phase: Tmax of ABBV-321 [ Time Frame: Up to 78 days post dose ]
    Time to Cmax (Tmax) of ABBV-321


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.



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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) or EGFR ligands:

Dose Escalation Phase:

  • Colorectal cancer/carcinoma (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 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.

Expanded Safety Phase:

  • Histologically or cytologically confirmed metastatic or unresectable CRC that is relapsed, refractory, or progressive following at least 2 prior but no more than 3 systemic cytotoxic regimens (excluding adjuvant or neoadjuvant therapy).
  • Must have measureable disease as per RECIST Version 1.1.
  • Participant had 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 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, or skull) within 21 days of the first dose of study drug.
  • Uncontrolled metastases to the central nervous system (CNS) or cytological/radiographic evidence of leptomeningeal carcinomatosis. Participants with brain metastases (other than leptomeningeal carcinomatosis) are eligible provided they do not require ongoing steroids and have shown clinical and radiographic stability for at least 28 days after definitive therapy. Primary glioblastoma is allowed.
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03234712


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
United States, Arkansas
Highlands Oncology Group /ID# 166132 Not yet recruiting
Fayetteville, Arkansas, United States, 72703-4005
United States, California
The Angeles Clinic and Researc /ID# 166133 Recruiting
Los Angeles, California, United States, 90025
United States, Illinois
Northwestern University /ID# 165191 Not yet recruiting
Chicago, Illinois, United States, 60611-2927
University of Chicago /ID# 166064 Not yet recruiting
Chicago, Illinois, United States, 60637
NorthShore Univ HealthSystem /ID# 201095 Not yet recruiting
Evanston, Illinois, United States, 60201
United States, New York
Columbia Univ Medical Center /ID# 167184 Not yet recruiting
New York, New York, United States, 10032-3725
United States, North Carolina
Duke Univ Med Ctr /ID# 166135 Recruiting
Durham, North Carolina, United States, 27710
United States, Rhode Island
Lifespan Cancer Institute /ID# 168600 Recruiting
Providence, Rhode Island, United States, 02903-4923
United States, Texas
South Texas Accelerated Research Therapeutics /ID# 166134 Recruiting
San Antonio, Texas, United States, 78229
Australia, New South Wales
Northern Cancer Institute /ID# 166138 Recruiting
St Leonards, New South Wales, Australia, 2065
Australia, Victoria
Austin Hospital /ID# 166137 Recruiting
Heidelberg, Victoria, Australia, 3084
Israel
Sheba Medical Center /ID# 166398 Recruiting
Ramat Gan, Israel, 5262100
Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03234712     History of Changes
Other Study ID Numbers: M16-438
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: December 18, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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)
EGFR ligands
Colorectal carcinoma (CRC)
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) or EGFR Ligands

Additional relevant MeSH terms:
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action