Clinical Trials /

Safety and Preliminary Efficacy of OBT076 in Recurrent/Metastatic CD205+ Solid Tumors and HER2-neg Breast Cancer

NCT04064359

Description:

The purpose of this study is to evaluate OBT076, which is a drug that combines an antibody with an anti-cancer drug. This class of drugs are called Antibody-Drug Conjugates (ADC). Antibodies are normally produced in the human body by the immune system to fight infections but can be designed to target cancer cells and deliver an anti-cancer drug. OBT076 is composed of an antibody that targets the CD205 protein on cancer cells and delivers an anti-cancer drug which can kill them. OBT076 is an "Investigational Drug", which means that it is still being studied and has not yet been approved by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory authorities to be prescribed by doctors for the treatment of metastatic or recurrent solid tumors. The use of OBT076 in this study is investigational. This is a Phase I research study designed to look at several dose levels of the study drug to find the highest dose level that is safe and well-tolerated (does not cause unacceptable side effects), and to examine the effects of the study drug in a small group of research participants. The study will also look at the effectiveness of OBT076 as an anti-cancer therapy. Once the optimal dose is determined and safety is assessed, additional research participants will be treated at the optimal dose level to further evaluate safety and effectiveness.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Preliminary Efficacy of OBT076 in Recurrent/Metastatic CD205+ Solid Tumors and HER2-neg Breast Cancer
  • Official Title: A Phase I, Open-label, Dose Finding Study to Assess the Safety, Tolerability, PK, and Preliminary Efficacy of OBT076, a CD205-directed ADC, in Recurrent and/or Metastatic CD205+ Solid Tumors and CD205+ HER2-negative Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: OBT076-001
  • NCT ID: NCT04064359

Conditions

  • Breast Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
OBT076, a CD205-directed antibody-drug conjugateMEN1309OBT076 Dose Escalation and Expansion

Purpose

The purpose of this study is to evaluate OBT076, which is a drug that combines an antibody with an anti-cancer drug. This class of drugs are called Antibody-Drug Conjugates (ADC). Antibodies are normally produced in the human body by the immune system to fight infections but can be designed to target cancer cells and deliver an anti-cancer drug. OBT076 is composed of an antibody that targets the CD205 protein on cancer cells and delivers an anti-cancer drug which can kill them. OBT076 is an "Investigational Drug", which means that it is still being studied and has not yet been approved by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory authorities to be prescribed by doctors for the treatment of metastatic or recurrent solid tumors. The use of OBT076 in this study is investigational. This is a Phase I research study designed to look at several dose levels of the study drug to find the highest dose level that is safe and well-tolerated (does not cause unacceptable side effects), and to examine the effects of the study drug in a small group of research participants. The study will also look at the effectiveness of OBT076 as an anti-cancer therapy. Once the optimal dose is determined and safety is assessed, additional research participants will be treated at the optimal dose level to further evaluate safety and effectiveness.

Detailed Description

      Study OBT076-001 is an open-label, Phase I, dose escalation and expansion clinical study of
      OBT076, a CD205-directed ADC, in CD205+ve, and HER2-ve metastatic breast cancer and recurrent
      and/or metastatic CD205+ve solid tumors. Part A, the dose escalation phase of the study, will
      explore escalating IV doses to determine the maximum tolerated dose (MTD) of OBT076.
      Approximately 20 subjects will be included in Part A of the study. Part B, the expansion
      phase of the study, will further evaluate the safety and preliminary efficacy of OBT076
      administered at or below the MTD in expansion cohorts. Approximately 50 subjects will be
      enrolled in Part B. Parts A and B will consist of 3 periods: Screening, Treatment, and
      Follow-up.
    

Trial Arms

NameTypeDescriptionInterventions
OBT076 Dose Escalation and ExpansionExperimentalOBT076 administered intravenously (IV) every 3 weeks in escalating dose cohorts during Part A and OBT076 administered at or below the MTD in the Part B expansion cohort.
  • OBT076, a CD205-directed antibody-drug conjugate

Eligibility Criteria

        Inclusion Criteria:

          1. Subject is ≥ 18 years of age (at the time of signing the ICF) with non-curative
             recurrent and/or metastatic solid tumors for which a standard therapy is not available
             or is no longer effective.

          2. Subject has histologically and/or cytologically confirmed solid tumors.

          3. Subject has recurrent and/or metastatic non-curative HER2-ve breast cancer (based on
             most recently analyzed biopsy) defined by ASCO-CAP guidelines as negative in situ
             hybridization test or an IHC status of 0, 1+, or 2+. If IHC is 2+, a negative in situ
             hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.

          4. Prior treatment with checkpoint inhibitors is allowed.

          5. Subject has tumor that is positive for CD205 antigen by IHC staining

          6. Subject has an ECOG performance status of 0-1.

          7. Subject has radiological documented measurable disease (i.e., at least 1 measurable
             lesion as per RECIST Version 1.1).

          8. Subject has adequate organ function

          9. Subject has adequate bone marrow function

         10. Subject understands and voluntarily signs an ICD prior to any study-related
             assessments/procedures are conducted.

         11. Subject is able to adhere to the study visit schedule and other protocol requirements.

        Exclusion Criteria:

          1. Subject has received any chemotherapy within 21 days prior to inclusion in the study.

          2. Subject has received another investigational therapy within 28 days.

          3. Subject has not recovered from the acute toxic effects (CTCAE grade ≤ 1) of prior
             anticancer therapy, radiation, or major surgery/significant trauma (except alopecia or
             other toxicities not considered a safety risk for the subject at the Investigator's
             discretion).

          4. Subject has had major surgery within 14 days prior to starting study treatment or has
             not recovered from major side effects.

          5. Subject has had radiotherapy ≤ 4 weeks prior to starting study drug.

          6. Subject has a history of, or current symptomatic brain metastasis.

          7. Subject has severe renal impairment (creatinine clearance < 30 mL/min).

          8. Subject has any other malignancy within 5 years prior to randomization

          9. Subject has a known or suspected hypersensitivity or other contraindication to any
             excipients used in the manufacture of OBT076.

         10. Subject has significant active cardiac disease within the previous 6 months including
             unstable angina or angina requiring surgical or medical intervention, significant
             cardiac arrhythmia, or NYHA class 3 or 4 congestive heart failure.

         11. Subject has a known history or current diagnosis of HIV infection, unless on triple
             antiviral treatment with undetectable viral load.

         12. Subject has any significant medical condition, laboratory abnormality, or psychiatric
             illness that would, in the Investigator's judgment, contraindicate subject
             participation in the study (e.g., history of thromboembolic event, cardiac
             dysfunction, chronic pancreatitis, chronic active hepatitis).

         13. Subject has any condition that confounds the ability to interpret data from the study.

         14. Subject is a female of childbearing potential.

         15. Subject is lactating or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events (AEs) as assessed by NCI CTCAE (Version 5)
Time Frame:1 year
Safety Issue:
Description:Assess incidence of all AEs by NCI CTCAE (Version 5) grades 1-5

Secondary Outcome Measures

Measure:Clinical Benefit Ratio (CBR)
Time Frame:2 years
Safety Issue:
Description:RECIST, Version 1.1
Measure:Overall Response Rate (ORR)
Time Frame:2 years
Safety Issue:
Description:RECIST, Version 1.1
Measure:Duration of Response (DoR)
Time Frame:2 years
Safety Issue:
Description:Kaplan-Meier methodology
Measure:Progression Free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Kaplan-Meier methodology
Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:Kaplan-Meier methodology
Measure:Area under the Plasma Concentration versus Time Curve (AUC) of OBT076
Time Frame:1 year
Safety Issue:
Description:Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076
Measure:Maximum Plasma Concentration [Cmax] of OBT076
Time Frame:1 year
Safety Issue:
Description:Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076
Measure:Time Taken to Reach the Maximum Plasma Concentration [Tmax] of OBT076
Time Frame:1 year
Safety Issue:
Description:Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076
Measure:Half-Life [T1/2] of OBT076
Time Frame:1 year
Safety Issue:
Description:Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076
Measure:Clearance (CL) of OBT076
Time Frame:1 year
Safety Issue:
Description:Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076
Measure:Volume of Distribution (Vd) of OBT076
Time Frame:1 year
Safety Issue:
Description:Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oxford BioTherapeutics Ltd

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