Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression

NCT ID: NCT04180371

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-07
• Study Completion Date: 2027-07-31

Brief Summary

This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known for expression of EphA2. The main goals of this study are to:

• Find the recommended dose(s) of BT5528 that can be given safely to participants alone and in combination with nivolumab
• Learn more about the side effects of BT5528
• Learn about how effective BT5528 is for the treatment of ovarian cancer, urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head and neck cancer (HNSCC), and gastric/upper gastrointestinal cancer.
• Learn more about BT5528 therapy alone and in combination with nivolumab.

Detailed Description

BT5528 consists of a bicyclic peptide (Bicycle®) which binds to EphA2, and is covalently attached to a spacer and a protease cleavable peptide linker attached to MMAE.

The Phase I/II multi-center, open-label trial will evaluate BT5528 administered once-weekly as a single agent and in combination with nivolumab. The Phase I portion is a dose escalation primarily designed to assess the safety and tolerability of BT5528 and to determine recommended Phase II dose(s) (RP2D). Following selection of a recommended Phase II dose(s) (RP2D), a dose expansion portion will be initiated with the primary objective of evaluating the clinical activity of BT5528.

Conditions

Advanced Solid Tumor Historically Known for High EphA2 Expression; Urothelial Cancer; Ovarian Cancer; Non-small Cell Lung Cancer; Head and Neck Cancer; Triple Negative Breast Cancer; Gastric/Upper Gastrointestinal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I - Dose escalation (BT5528)

Cohorts of participants will receive increasing doses of BT5528. It is expected that up to 72 participants will participate in this dose escalation arm.

Group Type: EXPERIMENTAL

BT5528

Intervention Type: DRUG

Participants will receive a 60-minute intravenous infusion of BT5528 once a week (Days 1, 8, 15, and 22) or every other week (Days 1 and 15) on a 4-week cycle at the selected dose.

Phase I - Dose escalation combination (BT5528 & nivolumab)

Cohorts of participants will receive increasing doses of BT5528 and a standard dose of nivolumab. It is expected that up to 24 participants will participate in this dose-escalation combination arm.

Group Type: EXPERIMENTAL

BT5528

Intervention Type: DRUG

Participants will receive a 60-minute intravenous infusion of BT5528 once a week (Days 1, 8, 15, and 22) or every other week (Days 1 and 15) on a 4-week cycle at the selected dose.

Nivolumab

Intervention Type: DRUG

Participants will receive nivolumab at 480mg intravenous infusion every 4 weeks.

Phase II - Dose expansion 1 (BT5528)

A cohort of participants will receive the selected dose of BT5528 as a monotherapy. It is expected that up to 164 patients have solid tumors (Cohort 1: urothelial cancers, Cohort 2: ovarian cancer, Cohort 3: non-small cell lung cancer, Cohort 4: head and neck cancer, Cohort 5: triple-negative breast cancer, and Cohort 6: gastric/upper gastrointestinal cancer) historically known for high expression of EphA2 will participate in this dose-expansion arm, Cohort 7: urothelial MMAE exposed, Cohort 8: head and neck squamous cell carcinoma

Group Type: EXPERIMENTAL

BT5528

Intervention Type: DRUG

Participants will receive a 60-minute intravenous infusion of BT5528 once a week (Days 1, 8, 15, and 22) or every other week (Days 1 and 15) on a 4-week cycle at the selected dose.

Interventions

BT5528

Participants will receive a 60-minute intravenous infusion of BT5528 once a week (Days 1, 8, 15, and 22) or every other week (Days 1 and 15) on a 4-week cycle at the selected dose.

Intervention Type: DRUG

Nivolumab

Participants will receive nivolumab at 480mg intravenous infusion every 4 weeks.

Intervention Type: DRUG

Other Intervention Names

Opdivo

Eligibility Criteria

Inclusion Criteria

• Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling or analyses
• At least 18 years-of-age at the time of signature of the informed consent form
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Acceptable renal, hepatic, hematologic and coagulation functions
• Negative pregnancy test for women of childbearing potential
• Male participants with female partners of childbearing potential and female participants of childbearing potential are required to follow highly effective contraception
• All patients must have tumor tissue (fresh or archived) available for analysis of EphA2 tumor expression and other biomarkers. In the absence of available tumor tissue, patients must be willing to undergo a biopsy to provide fresh tumor samples
• Life expectancy ≥12 weeks after the start of BT5528 treatment according to the Investigator's judgment.
• Must be willing and able to comply with the protocol and study procedures.

• Metastatic recurrent histologically confirmed malignant solid tumors historically known for high EphA2 tumor expression. Confirmation of EphA2 expression prior to enrollment is not required for participants with ovarian cancer and specific other individual tumor types.
• Exhausted all appropriate treatment options per local guidelines
• Participants with urothelial cancer who have at least 1 (but no more than 3) prior lines of systemic therapy.

• Participants with metastatic recurrent disease histologically confirmed to be non-small cell lung cancer, ovarian cancer, triple-negative breast cancer (TNBC), gastric/upper gastrointestinal (GI) cancer, head and neck (H&N) cancer, urothelial cancer are eligible and must have failed or are ineligible for all appropriate treatment options per local guidelines and must have evidence of radiographic progression on the most recent line of therapy
• Patients with urothelial cancer who have previously received treatment with enfortumab vedotin (EV) are eligible to the study. Patients who received EV and showed disease progression within 6 months of treatment start are planned for less than 50% of total patients enrolled in the cohort

Exclusion Criteria

• Chemotherapy treatments within 14 days prior to first dose of study treatment, other anticancer treatments, treatment within 28 days or 5 half-lives, whichever is the shorter
• Experimental treatments within 4 weeks of first dose of BT5528
• Prior toxicities must have resolved to Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 (except alopecia which can be Grade 2), or well-controlled Grade 2 hypothyroidism or Grade 2 adrenal insufficiency on appropriate therapy
• Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors of P-gp
• Known sensitivity to any of the ingredients of the investigational product or monomethyl auristatin E (MMAE)
• Any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with the patient's participation, or is not in the best interest of the patient to participate in the opinion of the investigator including but not limited to specific cardiovascular criteria
• Major surgery (excluding placement of vascular access) within 4 weeks of first dose of BT5528 study treatment and must have recovered adequately prior to starting study therapy
• Receipt of live vaccine within 30 days of study treatment
• Untreated CNS metastases or leptomeningeal disease
• Uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg that is not responsive to intervention) at screening or prior to initiation of study drug.
• History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with the patient's participation, or is not in the best interest of the patient to participate in the opinion of the Investigator including but not limited to:

(a) Patients with history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, congestive heart failure or symptoms of New York Heart Association Class III-IV documented within 6 months prior to first dose of BT5528 or: (i) Mean resting corrected QT interval (QTcF) >470 msec (ii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval (iii) Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third degree heart block

• Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). Note: Well controlled HIV will be allowed if the patient meets all the following criteria at inclusion:

1. CD4+ T-cell (CD4+) counts ≥350 cells/uL;

2. HIV viral load <400 copies/mL

3. Without a history of opportunistic infection within the last 12 months.

4. On established antiretroviral therapy (ART) for at least 4 weeks. Use of anti-retroviral therapy is permitted, but should be discussed with the Medical Monitor on a case-by-case basis.

• Patients with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody. Patients with a negative polymerase chain reaction (PCR) assay are permitted with appropriate antiviral therapy
• Active hepatitis C infection with positive viral load if hepatitis C virus (HCV) antibody positive (if antibody is negative then viral load not applicable). Patients who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of ≥12 weeks.
• Thromboembolic events and/or bleeding disorders 3 months (e.g., deep vein thrombosis [DVT] or pulmonary embolism [PE]) prior to first dose
• Prior history of pneumonitis with presence of residual symptoms
• History of another malignancy within 3 years before the first dose of BT5528, or any evidence of residual disease from a previously diagnosed malignancy (excluding adequately treated with curative intent basal cell carcinoma, squamous cell of the skin, cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in situ or ductal carcinoma in situ of the breast).
• Systemic anti-infective treatment or fever within the last 14 days prior to first dose of BT5528 study treatment
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

• Prior intolerance to immune checkpoint inhibitor
• Known hypersensitivity to checkpoint inhibitor therapy
• Prior organ transplant (including allogeneic)
• Diagnosis of clinically relevant immunodeficiency
• Active systemic infection requiring therapy
• More than 10 mg daily prednisone equivalent or other strong immunosuppressant
• History of autoimmune disease except alopecia, vitiligo, hypothyroidism, or adrenal insufficiency
• History of interstitial lung disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BicycleTx Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Meredith McKean, MD, MPH

Role: STUDY_CHAIR

Sarah Cannon and HCA Research Institute

Locations

California Cancer Associates for Research and Excellence, Inc.

Encinitas, California, United States

University of California - Irvine Medical Center

Orange, California, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Florida Cancer Specialists

Sarasota, Florida, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Stephenson Cancer Center (Oklahoma University)

Oklahoma City, Oklahoma, United States

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Institut Jules Bordet

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Antwerp University Hospital (UZA)

Edegem, , Belgium

Universitair Ziekenhuis Gent (UZ)

Ghent, , Belgium

Gachon University Gil Medical Center

Incheon, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Fundación Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Sarah Cannon Research Institute UK

London, United Kingdom, United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom, United Kingdom

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

The Leeds Teaching Hospitals NHS Trust Of Trust Headquarters, St James's University Hospital

Leeds, , United Kingdom

Sir Bobby Robson Cancer Trials Research Centre, The Northern Center for Cancer Care, Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Countries

United States; Belgium; South Korea; Spain; United Kingdom

Other Identifiers

BT5528-100

Identifier Type: -

Identifier Source: org_study_id