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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)

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:
  • Bladder Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Glioblastoma
  • Head and Neck Squamous Cell Carcinoma
  • Kidney Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Sarcoma
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)
  • 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)

Clinical Trial IDs

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

Conditions

  • Advanced Solid Tumors Cancer

Interventions

DrugSynonymsArms
ABBV-321Serclutamab TalirineABBV-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). The study will consist of 2 phases: Dose Escalation Phase and Expansion 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). (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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:AUCt for ABBV-321
Time Frame:Up to 78 days post dose
Safety Issue:
Description:Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321

Secondary Outcome Measures

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: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: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: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: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: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.
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.

Details

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

Trial 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)

Last Updated

November 14, 2019