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BT5528

Phase 1

Advanced Solid Tumor Historically Known for High EphA2 Expression | Small molecule | Oncology |Bicycle Therapeutics plc|Last Updated: Nov 17, 2025

Target and mechanism

Molecular targetEphA2
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment288

FDA Designations

No designations recorded

Clinical trial landscape

BT5528 · 1 trial · 7 indications

Phase 1 1
NCT04180371Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 ExpressionAdvanced Solid Tumor Historically Known for High EphA2 Expression
ACTIVE NOT_RECRUITING288 Analytics
PHASE1ACTIVE NOT_RECRUITING
Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression
Advanced Solid Tumor Historically Known for High EphA2 ExpressionUnlock trial analytics

Study Endpoints

Primary Endpoints

Part A-1 and A-2(escalations): Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events
From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose

Safety reported as incidence of treatment-emergent adverse events

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
At the end of Cycle 1 (each cycle is 28 days)

Maximum Tolerated Dose (MTD)

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
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)

Objective Response Rate (ORR)

Part B: Duration of response by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
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)

Duration of Response (DOR)

Part B: Clinical benefit rate by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
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)

Clinical benefit rate

Part B: Time to tumor progression by RECIST 1.1 in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
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)

Time to Progression (TTP)

Part B: Progression-free survival by RECIST 1.1 in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
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)

Progression free survival (PFS)

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
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)

Progression free survival (PFS)

Part B: Overall survival (OS) at 1 year in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent

Overall survival (OS)

Secondary Endpoints

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
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
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
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
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Phase I - Dose escalation (BT5528)EXPERIMENTALCohorts of participants will receive increasing doses of BT5528. It is expected that up to 72 participants will participate in this dose escalation arm.
Phase I - Dose escalation combination (BT5528 & nivolumab)EXPERIMENTALCohorts 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.
Phase II - Dose expansion 1 (BT5528)EXPERIMENTALA 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

Interventions

NameTypeDescription
BT5528DRUGParticipants 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.
NivolumabDRUGParticipants will receive nivolumab at 480mg intravenous infusion every 4 weeks.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites28

General Inclusion: * 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 * Eas...

Countries:United StatesBelgiumSouth KoreaSpainUnited Kingdom
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Recent Changes (Last 90 Days)

LOWMay 26, 2026NCT04180371primaryCompletionDate: changed
LOWMay 24, 2026NCT04180371studyFirstPostDate: changed

Frequently asked questions about BT5528

What is BT5528 used for?

BT5528 is an investigational small molecule being developed for the treatment of advanced solid tumors historically known for high EphA2 expression, including urothelial cancer, ovarian cancer, non-small cell lung cancer, head and neck cancer, triple negative breast cancer, and gastric/upper gastrointestinal cancer.

What does BT5528 target?

BT5528 targets EphA2, a receptor tyrosine kinase that is overexpressed in certain solid tumors. By binding to EphA2, BT5528 is designed to deliver a cytotoxic payload specifically to cancer cells that express this target, potentially reducing damage to healthy tissues.

Who makes BT5528?

BT5528 is being developed by Bicycle Therapeutics plc, a biopharmaceutical company traded on the NASDAQ under the ticker symbol BCYC. The company is conducting clinical trials to evaluate the safety and efficacy of BT5528 in patients with advanced solid tumors.

What phase is BT5528 in?

BT5528 is currently in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The ongoing Phase 1 trial is actively enrolling participants, though recruitment is not yet complete.

What clinical trials is BT5528 in?

BT5528 is being studied in a single Phase 1 clinical trial with the identifier NCT04180371. This trial, titled 'Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression,' is enrolling approximately 288 participants across the United States, Belgium, South Korea, Spain, and the United Kingdom.

Is BT5528 the same as any other drug?

BT5528 is the sole name provided for this investigational agent. No alternative names or aliases have been reported for this drug in the available clinical trial information.