Advanced Solid Tumor Historically Known for High EphA2 ExpressionPhase 1/2NCT04180371
Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression
A Phase 1/2 study testing BT5528 and Nivolumab in people with Advanced Solid Tumor Historically Known for High EphA2 Expression and Urothelial Cancer, run by BicycleTx Limited at 28 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor Historically Known for High EphA2 Expression, Urothelial Cancer, Ovarian Cancer
- What is being tested?
- BT5528 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 288 participants
- Where
- 28 sitesin 5 countries
- Study dates
- 7 Nov 2019to 31 Jul 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
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- 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:
- 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:
- CD4+ T-cell (CD4+) counts ≥350 cells/uL;
- HIV viral load <400 copies/mL
- Without a history of opportunistic infection within the last 12 months.
- 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.
- Additional Exclusion Criteria (BT5528 in combination with nivolumab):
- 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
Trial locations and contacts
28 sites in 5 countries.
28 sites in 5 countries
United States12 sites
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
California Cancer Associates for Research and Excellence, Inc.
Encinitas, California, 92024
Virginia Cancer Specialists
Fairfax, Virginia, 22031
MD Anderson Cancer Center
Houston, Texas, 77030
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Sarah Cannon and HCA Research Institute
Nashville, Tennessee, 37221
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Stephenson Cancer Center (Oklahoma University)
Oklahoma City, Oklahoma, 73104
University of California - Irvine Medical Center
Orange, California, 92868
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Florida Cancer Specialists
Sarasota, Florida, 34232
Spain5 sites
Institut Catala d'Oncologia - L'Hospitalet
Barcelona, 08908
Hospital Universitario Vall d'Hebron
Barcelona, 8035
Hospital Fundación Jimenez Diaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Centro Integral Oncologico Clara Campal
Madrid, 28050
United Kingdom5 sites
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
The Leeds Teaching Hospitals NHS Trust Of Trust Headquarters, St James's University Hospital
Leeds, LS9 7TF
Sarah Cannon Research Institute UK
London, United Kingdom, W1G 6AD
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sir Bobby Robson Cancer Trials Research Centre, The Northern Center for Cancer Care, Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Belgium4 sites
Institut Jules Bordet
Brussels, 1070
Cliniques Universitaires Saint-Luc
Brussels
Antwerp University Hospital (UZA)
Edegem
Universitair Ziekenhuis Gent (UZ)
Ghent, 9000
South Korea2 sites
Gachon University Gil Medical Center
Incheon, 21565
Severance Hospital, Yonsei University Health System
Seoul, 3722
About this study
Official title: Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients With Advanced Malignancies Associated With EphA2 Expression
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.
Read the 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
- Being tested
- BT5528, Nivolumab
- Keywords
- EphA2, ovarian cancer, urothelial cancer, bladder cancer, NSCLC, TNBC, gastric cancer, GEJ cancer, HNSCC
- Medical subject headings
- Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung, Head and Neck Neoplasms, Triple Negative Breast Neoplasms, Gastrointestinal Neoplasms, Urinary Bladder Neoplasms, Stomach Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BT5528Drug
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.
NivolumabDrug
Also called Opdivo
Participants will receive nivolumab at 480mg intravenous infusion every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Phase I - Dose escalation (BT5528) | Experimental | Cohorts of participants will receive increasing doses of BT5528. It is expected that up to 72 participants will participate in this dose escalation arm. Receives: Drug: BT5528 |
| Phase I - Dose escalation combination (BT5528 & nivolumab) | Experimental | 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. Receives: Drug: BT5528; Drug: Nivolumab |
| Phase II - Dose expansion 1 (BT5528) | Experimental | 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 Receives: Drug: BT5528 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A-1 and A-2(escalations): Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events
Safety reported as incidence of treatment-emergent adverse events
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose
Part A-1 and A-2 (escalations): Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities from BT5528 treatment alone and in combination with nivolumab
Maximum Tolerated Dose (MTD)
Measured: At the end of Cycle 1 (each cycle is 28 days)
Part B: Objective response rate by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 tumor expression receiving BT5528 treatment
Objective Response Rate (ORR)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Part B: Duration of response by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
Duration of Response (DOR)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Part B: Clinical benefit rate by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
Clinical benefit rate
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Part B: Time to tumor progression by RECIST 1.1 in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
Time to Progression (TTP)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Part B: Progression-free survival by RECIST 1.1 in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
Progression free survival (PFS)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Part B: PFS at 6 months by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
Progression free survival (PFS)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months)
Part B: Overall survival (OS) at 1 year in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
Overall survival (OS)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent
Secondary outcomes (17)
Part A-1 and A-2 (escalations): Objective response rate (ORR) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Objective Response Rate (ORR)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part A-1 and A-2 (escalations): Duration of response (DOR) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Duration of Response (DOR)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part A-1 and A-2 (escalations): Clinical benefit rate (CBR) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Clinical benefit rate (CBR)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part A-1 and A-2 (escalations): Time to tumor progression (TTP) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time to progression (TTP)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part A-1 and A-2 (escalations): Progression-free survival (PFS) time by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Progression free survival (PFS)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part A-1 and A-2 (escalations): Progression free survival at 6 months by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Progression free survival (PFS)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months)
Part A-1 and A-2 (escalations): Overall survival time at 12 months in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Overall survival (OS)
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent (assessed every 3 months up to 12 months
Part B: Determination of the number of participants with advanced solid tumors historically known for high expression of EphA2 receiving BT5528 with treatment-emergent adverse events
Safety reported as incidence of treatment-emergent adverse events
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose
All parts: Determine the plasma concentrations of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
plasma concentrations of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
Measured: From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
All parts: Determine the plasma concentrations of MMAE in plasma from all participants taking BT5528 alone and in combination with nivolumab
plasma concentrations of MMAE in plasma from all participants taking BT5528 alone and in combination with nivolumab
Measured: From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
All parts: Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT5528 alone and in combination with nivolumab
Measured: From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
Part B: The association between EphA2 expression level and objective response rate (ORR) per RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
To investigate if the high expression of EphA2 is associated with high ORR per RECIST 1.1 participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part B: The association between EphA2 expression level and duration of response (DOR) by RECIST 1.1 and per EphA2 expression in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
To investigate if the high expression of EphA2 is associated with high DOR per RECIST 1.1 participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part B: The association between EphA2 expression level and clinical benefit rate (CBR) per RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
To investigate if the high expression of EphA2 is associated with high CBR per RECIST 1.1 participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part B: The association between EphA2 expression level and time to tumor progression (TTP) per RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
To investigate if the high expression of EphA2 is associated with long TTP per RECIST 1.1 participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part B: The association between EphA2 expression level and progression-free survival (PFS) at 6 months by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
To investigate if the high expression of EphA2 is associated with long PFS at 6 months per RECIST 1.1 participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Part B: The association between EphA2 expression level and overall survival (OS) at 1 year by RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
To investigate if the high expression of EphA2 is associated with long OS at 1 year per RECIST 1.1 participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment
Measured: From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent (assessed every 3 months up to 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2019
- Study start7 Nov 2019
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid Tumor Historically Known for High EphA2 ExpressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 288 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BicycleTx Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Meredith McKean, MD, MPH, Study chair, Sarah Cannon and HCA Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04180371
- Sponsor's protocol ID
- BT5528-100
- Status last verified
- Oct 2026
- First submitted
- 19 Nov 2019
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No