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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04064359
Recruitment Status : Recruiting
First Posted : August 21, 2019
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
Oxford BioTherapeutics Ltd

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Solid Tumor Drug: OBT076, a CD205-directed antibody-drug conjugate Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 25, 2019
Estimated Primary Completion Date : January 15, 2021
Estimated Study Completion Date : February 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: OBT076 Dose Escalation and Expansion
OBT076 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.
Drug: OBT076, a CD205-directed antibody-drug conjugate
Intravenous (IV) infusion of OBT076 every 3 weeks.
Other Name: MEN1309




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) as assessed by NCI CTCAE (Version 5) [ Time Frame: 1 year ]
    Assess incidence of all AEs by NCI CTCAE (Version 5) grades 1-5

  2. Percentage of subjects with dose-limiting toxicities (DLTs) as assessed by NCI CTCAE (Version 5) [ Time Frame: 1 year ]
    DLTs defined by NCI CTCAE (Version 5) grades 3-4, with exceptions for duration


Secondary Outcome Measures :
  1. Clinical Benefit Ratio (CBR) [ Time Frame: 2 years ]
    RECIST, Version 1.1

  2. Overall Response Rate (ORR) [ Time Frame: 2 years ]
    RECIST, Version 1.1

  3. Duration of Response (DoR) [ Time Frame: 2 years ]
    Kaplan-Meier methodology

  4. Progression Free Survival (PFS) [ Time Frame: 2 years ]
    Kaplan-Meier methodology

  5. Overall Survival (OS) [ Time Frame: 2 years ]
    Kaplan-Meier methodology

  6. Area under the Plasma Concentration versus Time Curve (AUC) of OBT076 [ Time Frame: 1 year ]
    Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076

  7. Maximum Plasma Concentration [Cmax] of OBT076 [ Time Frame: 1 year ]
    Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076

  8. Time Taken to Reach the Maximum Plasma Concentration [Tmax] of OBT076 [ Time Frame: 1 year ]
    Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076

  9. Half-Life [T1/2] of OBT076 [ Time Frame: 1 year ]
    Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076

  10. Clearance (CL) of OBT076 [ Time Frame: 1 year ]
    Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076

  11. Volume of Distribution (Vd) of OBT076 [ Time Frame: 1 year ]
    Statistics including number of subjects (N), mean, standard deviation, CV%, geometric mean, geometric CV%, median, minimum, and maximum will be provided for OBT076


Other Outcome Measures:
  1. Quantification of Serum Protein [ Time Frame: 2 years ]
    Enzyme-linked Immunosorbant Assay (ELISA)

  2. Quantification of Peripheral Blood CD205+ Cells [ Time Frame: 2 years ]
    Flow Cytometry

  3. Quantification of Immune Cells (ICs) in Tumor Microenvironment (TME) [ Time Frame: 2 years ]
    Immunohistochemistry



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  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.

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): NCT04064359


Contacts
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Contact: Medical Monitor +1 408 960 7461 Info-OBT076@Oxfordbiotherapeutics.com

Locations
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United States, California
Cedars-Sinai Recruiting
Los Angeles, California, United States, 90048
Contact: Kari Kayser, BSN, RN, CCRP       Kari.kayser@cshs.org   
Principal Investigator: Monica Mita, MD         
UCLA Recruiting
Santa Monica, California, United States, 90404
Contact: Suzanne Nichols, RN       snichols@mednet.ucla.edu   
Principal Investigator: Lee Rosen, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Solmaz Sahebjam, MD       Solmaz.Sahebjam@Moffitt.org   
Principal Investigator: Solmaz Sahebjam, MD         
United States, New Mexico
Quantum Santa Fe Recruiting
Santa Fe, New Mexico, United States, 87505
Contact: Chimela Ohaji, MBBCh MA BSc    505-913-8935    Chimela.Ohaji@stvin.org   
Principal Investigator: Olivier Rixe, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Nurse Navigator       Lo2345@cumc.columbia.edu   
Principal Investigator: Gary Schwartz, MD         
Sponsors and Collaborators
Oxford BioTherapeutics Ltd
Investigators
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Principal Investigator: Gary Schwartz, MD Columbia University
Principal Investigator: Solmaz Sahebjam, MD Moffitt Cancer Center
Principal Investigator: Olivier Rixe, MD Quantum Santa Fe
Principal Investigator: Monica Mita, MD Cedars-Sinai
Principal Investigator: Lee Rosen, MD University of California, Los Angeles
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Responsible Party: Oxford BioTherapeutics Ltd
ClinicalTrials.gov Identifier: NCT04064359    
Other Study ID Numbers: OBT076-001
First Posted: August 21, 2019    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs