Clinical Trials /

A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors

NCT04424641

Description:

The purpose of the trial is to evaluate the safety, determine the recommended phase 2 dose, and assess preliminary clinical activity of GEN1044 in subjects with solid tumors.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Esophageal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Malignant Uterine Neoplasm
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors
  • Official Title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1044 in Subjects With Malignant Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GCT1044-01
  • NCT ID: NCT04424641

Conditions

  • Dose Escalation Part: Locally Advanced or Metastatic Solid Tumor(s)
  • Expansion Part: Prostate Cancer
  • Expansion Part: Esophageal Cancer
  • Expansion Part: Triple Negative Breast Cancer (TNBC)
  • Expansion Part: Squamous Cell Carcinoma of Head and Neck (SCCHN)
  • Expansion Part: Non-small Cell Lung Cancer (NSCLC)
  • Expansion Part: Bladder Cancer
  • Expansion Part: Uterine Cancer

Interventions

DrugSynonymsArms
GEN1044 is an IgG1 bispecific antibody targeting CD3 and 5T4.Treatment

Purpose

The purpose of the trial is to evaluate the safety, determine the recommended phase 2 dose, and assess preliminary clinical activity of GEN1044 in subjects with solid tumors.

Detailed Description

      The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two
      parts: a dose escalation part (phase 1) and an expansion part (phase 2a). The expansion part
      of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined
      from phase 1.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalOpen Label, single arm where GEN1044 will be administered
  • GEN1044 is an IgG1 bispecific antibody targeting CD3 and 5T4.

Eligibility Criteria

        Key Inclusion Criteria:

        Dose Escalation Part:

        • Subject with locally advanced or metastatic solid tumor(s) (excluding subjects with
        primary central nervous system [CNS] tumors), who has experienced disease progression while
        on standard therapy or is intolerant of, or not eligible for, standard therapy.

        Expansion Part:

        • Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the
        following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, Triple Negative
        Breast Cancer (TNBC), Squamous Cell Carcinoma of the Head and Neck (SCCHN), Non-small Cell
        Lung Cancer (both adenocarcinoma (ACC) and squamous cell carcinoma (SCC) (NSCLC/ACC and
        NSCLC/SCC), Bladder Cancer.

        Both Parts:

          -  Must sign an informed consent form (ICF) indicating that he or she understands the
             purpose of, and procedures required for the trial, and is willing to participate in
             the trial prior to any trial related assessments or procedures.

          -  Must have measurable disease according to response assessment criteria relevant to the
             tumor type.

          -  Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of
             0-1 at Screening and on C1D1.

          -  A woman of reproductive potential must agree to use adequate contraception during the
             trial and for 4 months after the last GEN1044 administration. Adequate contraception
             is defined as highly effective methods of contraception.

        Key Exclusion Criteria (both parts):

          1. Has an uncontrolled intercurrent illness, including but not limited to:

               1. Ongoing or active infection requiring intravenous treatment with anti-infective
                  therapy

               2. Symptomatic congestive heart failure (grade III or IV as classified by the New
                  York Heart Association), unstable angina pectoris or cardiac arrhythmia.

               3. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or
                  diastolic blood pressure ≥100 mmHg, despite optimal medical management.

               4. Ongoing or recent evidence of significant autoimmune disease Subjects with a
                  history of grade 3 or higher irAEs that led to treatment discontinuation.

               5. Subjects with a prior history of myositis, Guillain-Barré syndrome, or myasthenia
                  gravis of any grade.

               6. History of chronic liver disease or evidence of hepatic cirrhosis.

               7. History of non-infectious pneumonitis that has required steroids, or currently
                  has pneumonitis.

               8. History of organ allograft (except for corneal transplant) or autologous or
                  allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to
                  the first dose of GEN1044.

               9. Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.

          2. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or
             symptomatic brain metastases or stroke.

          3. Prior therapy:

             Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration.
             Palliative radiotherapy will be allowed.

          4. Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of
             the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from
             previous anti-cancer therapies that have not resolved.

          5. Has a history of ≥ grade 2 cytokine release syndrome (CRS) with other CD3-based
             bispecifics, or a history of ≥ grade 3 allergic reactions to monoclonal antibody
             therapy as well as known or has known allergies, hypersensitivity, or intolerance to
             GEN1044 or its excipients.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation Part: Dose Limiting Toxicities (DLTs)
Time Frame:DLTs will be assessed during the first cycle (21 days) in each cohort
Safety Issue:
Description:To assess recommended phase 2 dose

Secondary Outcome Measures

Measure:To establish the pharmacokinetic profile (PK) profile of GEN1044
Time Frame:Assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Rate at which the drug is removed from the body (clearance)
Measure:To establish the PK profile of GEN1044
Time Frame:Assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Amount of drug in the body (volume of distribution)
Measure:To establish the PK profile of GEN1044
Time Frame:Assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Area-under-the-concentration-time curve (AUC0-C last)
Measure:To establish the PK profile of GEN1044
Time Frame:Assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Maximum concentration of GEN1044 (Cmax) after dosing
Measure:To establish the PK profile of GEN1044
Time Frame:Assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Time after dosing at which the maximum drug concentration was observed (Tmax)
Measure:To establish the PK profile of GEN1044
Time Frame:PK parameter will be assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Time after dosing at which the lowest drug concentration is observed before the next dose is administered (CTrough)
Measure:To establish the PK profile of GEN1044
Time Frame:PK parameter will be assed throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Elimination half-life of the drug (T1/2)
Measure:Evaluate immunogenicity of GEN1044
Time Frame:ADA are collected throughout trial until the end of the safety follow-up period (30 days after last dose)
Safety Issue:
Description:Anti-drug antibody response (ADA)
Measure:Expansion Part: Evaluate efficacy
Time Frame:Assessment will be made through trial completion, up to 5 years after last patient first visit.
Safety Issue:
Description:Progression free survival (Overall survival)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Genmab

Last Updated

June 5, 2020