Clinical Trials /

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

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Glioblastoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: M16-438
  • NCT ID: NCT03234712

Conditions

  • Advanced Solid Tumors With Overexpression of Epidermal Growth Factor Receptor (EGFR) or EGFR Ligands

Interventions

DrugSynonymsArms
ABBV-321ABBV-321

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ABBV-321ExperimentalABBV-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.
  • ABBV-321

Eligibility 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), or squamous non-small cell lung cancer (sqNSCLC)

          -  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 systemic regimens in
             the metastatic setting.

        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 < 35% 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 have discontinued EGFR targeted therapy prior to the first dose of
             study drug.

          -  Participant must not have been treated with any investigational drug within 30 days or
             5 half-lives of the drug (whichever is longer) prior to the first dose of study drug,
             or is currently enrolled in another clinical study.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321
Time Frame:Minimum first cycle of dosing (up to 28 days)
Safety Issue:
Description:The MTD of ABBV-321 will be determined during the dose escalation phase of the study.

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Advanced Solid Tumors
  • EGFR ligands
  • Squamous cell carcinoma of the head and neck (HNSCC)
  • Glioblastoma (GBM)
  • Colorectal carcinoma (CRC)
  • Cancer
  • Epidermal Growth Factor Receptor (EGFR)
  • Squamous non-small cell lung cancer (sqNSCLC)

Last Updated

November 8, 2017