Safety and Preliminary Efficacy of OBT076 in Recurrent/Metastatic CD205+ Solid Tumors

NCT04064359 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OBT076-001
• Study Type: interventional
• Target: 200
• Locations: 5 countries
• Sites: 27

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs) as assessed by NCI CTCAE (Version 5)

  Assess incidence of all AEs by NCI CTCAE (Version 5) grades 1-5

  1 year

• Percentage of subjects with dose-limiting toxicities (DLTs) as assessed by NCI CTCAE (Version 5)

  DLTs defined by NCI CTCAE (Version 5) grades 3-4, with exceptions for duration

  1 year

Secondary Outcomes (11)

• Clinical Benefit Ratio (CBR)

  2 years

• Overall Response Rate (ORR)

  2 years

• Duration of Response (DoR)

  2 years

• Progression Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

Other Outcomes (3)

• Quantification of Serum Protein

  2 years

• Quantification of Peripheral Blood CD205+ Cells

  2 years

• Quantification of Immune Cells (ICs) in Tumor Microenvironment (TME)

  2 years

Study Arms (1)

OBT076 Dose Escalation and Expansion

EXPERIMENTAL

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. In Part C sequential administration of OBT076 administered at the recommended phase 2 dose (RP2D) followed by Balstilmab. Part D will evaluate the safety, tolerability, preliminary efficacy of OBT-076 in combination with Balstilmab. Part E will evaluate the safety, tolerability and preliminary efficacy of OBT076 as a triple combination regimen with balstilimab and gemcitabine in patients with metastatic NSCLC (Cohort E1) or locally-advanced/metastatic urothelial cancer Cohort E2)

Drug: OBT076, a CD205-directed antibody-drug conjugate

Interventions

OBT076, a CD205-directed antibody-drug conjugate DRUG

Intravenous (IV) infusion of OBT076 every 3 weeks.

Also known as: MEN1309

OBT076 Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subject has histologically and/or cytologically confirmed solid tumors.
• Subject with Breast cancer:
• Subject with hormone-receptor positive (as per local laboratory) recurrent locally advanced or metastatic breast cancer, regardless of HER2 status, must have received at least two prior lines of endocrine therapy in the adjuvant or metastatic setting, either as monotherapy or in combination with targeted therapy
• Subject with recurrent locally advanced or metastatic non-curative HER2 negative breast cancer (based on most recently analyzed biopsy), HER2 status is defined as per ASCO-CAP guidelines as negative, if in situ hybridization test or IHC status is 0, 1+, or 2+.
• Subject with triple negative breast cancer are eligible after at least one prior line of cytotoxic chemotherapy in the metastatic setting.
• Subject with prior adjuvant or neoadjuvant chemotherapy allowed.
• Subject has received a maximum of two prior lines of cytotoxic chemotherapy in the metastatic setting. Subject who received three up to five prior lines of cytotoxic chemotherapy in the metastatic setting are eligible, if the last administration of cytotoxic chemotherapy was at least 12 weeks prior to Cycle 1 Day 1
• Subject has tumor that is positive for CD205 antigen by IHC staining
• Subject has an ECOG performance status of 0-1.
• Subject has radiological documented measurable disease (i.e., at least 1 measurable lesion as per RECIST Version 1.1).
• Subject has adequate organ function
• Subject has adequate bone marrow function
• Subject understands and voluntarily signs an ICD prior to any study-related assessments/procedures are conducted.
• Subject is able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Subject has received any chemotherapy within 28 days prior to Cycle 1 Day 1.
• Subject has received any other systemic anticancer therapy within 28 days or 5 half-lives of Cycle 1 Day 1.
• Subject has symptomatic visceral crisis requiring chemotherapy per Investigator judgment for non TNBC.
• Subject with colorectal cancer and pancreatic cancer are not eligible for the study.
• Subject with peritoneal involvement, i.e., peritoneal carcinomatosis, are not eligible for the study.
• 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).
• Subject has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
• Subject has had radiotherapy ≤ 4 weeks prior to starting study drug.
• Subject has a history of, or current symptomatic brain metastasis.
• Subject has any other malignancy within 5 years prior to randomization
• Subject has a known or suspected hypersensitivity or other contraindication to any excipients used in the manufacture of OBT076.
• Subject has significant medical condition, laboratory abnormality, or psychiatric illness that would, in the Investigator's judgment, contraindicate patient participation in the study (e.g., history of thromboembolic event, cardiac dysfunction, chronic pancreatitis, chronic active hepatitis)
• Subject has severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine \<7 days before Cycle 1 Day 1
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is lactating or breastfeeding.

Sponsors & Collaborators

• Oxford BioTherapeutics Ltd: lead

Study Sites (27)

Mayo Clinic

Phoenix, Arizona, 85084, United States

COMPLETED

Cedars-Sinai

Los Angeles, California, 90048, United States

COMPLETED

UCLA

Santa Monica, California, 90404, United States

COMPLETED

Moffitt Cancer Center

Tampa, Florida, 33612, United States

COMPLETED

The State University of Iowa

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

St. Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

COMPLETED

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

COMPLETED

Quantum Santa Fe

Santa Fe, New Mexico, 87505, United States

COMPLETED

Columbia University Medical Center

New York, New York, 10032, United States

COMPLETED

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

COMPLETED

Institut Jules Bordet

Brussels, Belgium

RECRUITING

AZ Groeninge

Kortrijk, Belgium

COMPLETED

Institut Paoli Calmettes

Marseille, France

RECRUITING

GHP Saint-Joseph

Paris, France

RECRUITING

Hopital Saint Antoine

Paris, France

COMPLETED

Hopital Saint Louis

Paris, France

RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

ICANS - Institut de cancérologie Strasbourg

Strasbourg, France

RECRUITING

Institut Gustave Roussy - IGR

Villejuif, France

RECRUITING

University General Hospital Attikon

Chaïdári, Athens, 12462, Greece

RECRUITING

Metropolitan Hospital

Athens, Greece

COMPLETED

Sotiria General Hospital

Athens, Greece

RECRUITING

University General Hospital of Heraklion

Heraklion, Greece

RECRUITING

EuroMedica

Thessaloniki, GR-54645, Greece

COMPLETED

START Barcelona HM Nou Delfos

Barcelona, 08023, Spain

RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

University Hospital Marqués de Valdecilla

Santander, 39008, Spain

RECRUITING

Central Study Contacts

Medical Monitor

CONTACT

+44 (0)1235 861770; OBT076-001@oxfordbiotherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2019
• First Posted: August 21, 2019
• Study Start: July 25, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); GR (5); ES (3); BE (2); FR (7)