Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression
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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: NCT04180371 |
Recruitment Status :
Recruiting
First Posted : November 27, 2019
Last Update Posted : January 20, 2021
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This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors that are identified as positive for EphA2 expression. The main goals of this study are to:
- Find the recommended dose of BT5528 that can be given safely to participants alone and in combination with nivolumab
- Learn more about the side effects of BT5528
- Learn more about BT5528 therapy alone and in combination with nivolumab.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced Solid Tumor Identified as Positive for EphA2 Tumor Expression by Central Laboratory (Phase 1) Non Small Cell Lung Cancer Identified as Positive for EphA2 Tumor Expression by Central Laboratory (Phase 2) | Drug: BT5528 Drug: Nivolumab | Phase 1 Phase 2 |
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 a recommended Phase II dose (RP2D). Following selection of a recommended Phase II dose (RP2D), a dose expansion portion will be initiated with the primary objective of evaluating the clinical activity of BT5528.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 166 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | November 7, 2019 |
Estimated Primary Completion Date : | December 31, 2022 |
Estimated Study Completion Date : | December 31, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Phase I - Dose escalation (BT5528)
Cohorts of participants will receive increasing doses of BT5528. It is expected that up to 48 participants will participate in this dose escalation arm.
|
Drug: 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. |
Experimental: 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.
|
Drug: 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. Drug: Nivolumab Participants will receive nivolumab at 480mg intravenous infusion every 4 weeks.
Other Name: Opdivo |
Experimental: 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 40 patients with non-small cell lung cancer (NSCLC) with EGFR mutation and confirmed EphA2 tumor expression will participate in this dose expansion arm.
|
Drug: 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. |
Experimental: Phase II - Dose expansion combination (BT5528 & nivolumab)
A cohort of participants will receive the selected dose of BT5528 in combination with a standard dose of nivolumab. It is expected that up to 14 participants with non-small cell lung cancer without EGFR mutation and confirmed EphA2 tumor expression will participate in this dose expansion arm.
|
Drug: 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. Drug: Nivolumab Participants will receive nivolumab at 480mg intravenous infusion every 4 weeks.
Other Name: Opdivo |
Experimental: Phase II - Dose expansion 2 (BT5528)
A cohort of participants will receive the selected dose of BT5528 as a monotherapy. It is expected that up to 40 patients with NSCLC without EGFR mutation and confirmed EphA2 tumor expression will participate in this dose expansion arm.
|
Drug: 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. |
- Phase I: Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events [ Time Frame: 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
- Phase I: Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities from BT5528 treatment alone and in combination with nivolumab [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]Maximum Tolerated Dose (MTD)
- Phase II: Objective response rate by RECIST 1.1 in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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) ]Objective Response Rate (ORR)
- Phase II: Duration of response by RECIST 1.1 in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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 ]Duration of Response (DOR)
- Phase II: Clinical benefit rate by RECIST 1.1 in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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 ]Clinical benefit rate
- Phase II: Time to tumor progression by RECIST 1.1 in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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 ]Time to Progression (TTP)
- Phase II: Progression free survival by RECIST 1.1 in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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 ]Progression free survival (PFS)
- Phase II: PFS at 6 months by RECIST 1.1 in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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)
- Phase II: Overall survival at 1 year in participants with adenocarcinoma non-small cell lung cancer or other identified tumor subtypes which are positive for EphA2 tumor expression receiving BT5528 treatment alone and in combination with nivolumab [ Time Frame: 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 for up to 1 year) ]Overall survival (OS)
- Phase I: Objective response rate by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]Objective Response Rate (ORR)
- Phase I: Duration of response by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]Duration of Response (DOR)
- Phase I: Clinical benefit rate by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]Clinical benefit rate
- Phase I: Time to tumor progression by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]Time to progression (TTP)
- Phase I: Progression free survival time by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]Progression free survival (PFS)
- Phase I: 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 [ Time Frame: 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)
- Phase I: Overall survival time at 12 months in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]Overall survival (OS)
- Phase II: Determination of the number of participants with non-small cell lung cancer or other identified tumor subtypes positive for EphA2 tumor expression receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose ]
- All phases: Determine the plasma concentrations of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab [ Time Frame: 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 phases: Determine the plasma concentrations of MMAE in plasma from all participants taking BT5528 alone and in combination with nivolumab [ Time Frame: 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 phases: Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT5528 alone and in combination with nivolumab [ Time Frame: 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 ]

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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
- 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
- Availability of archived tumor samples or willingness to provide fresh tumor biopsy during screening for EphA2 assessment
Additional inclusion criteria for Phase I (dose escalation phase, with BT5528 alone or in combination with nivolumab):
- Metastatic recurrent histologically confirmed malignant solid tumors confirmed to have 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
Additional inclusion criteria for Phase II (dose expansion phase, with BT5528 alone or in combination with nivolumab):
- Participants with metastatic recurrent disease histologically confirmed to be adenocarcinoma subtype of NSCLC (adeno-NSCLC) or other tumor subtypes are eligible and must have exhausted all appropriate treatment options per local guidelines including progression on or after platinum-based chemotherapy and appropriate therapies for driver mutations (if applicable).
- Confirmed EphA2 tumor expression prior to enrollment, unless waived for specific tumor types
Exclusion criteria (all participants):
- 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
- Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors of P-gp
- Uncontrolled, symptomatic brain metastases
- 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
- Thromboembolic events and/or bleeding disorders 3 months (e.g., deep vein thrombosis [DVT] or pulmonary embolism [PE]) prior to first dose
Additional Exclusion Criteria (BT5528 in combination with nivolumab):
- 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 or vitiligo
- History of interstitial lung disease

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): NCT04180371
Contact: Bicycle Tx Limited | 617-945-8155 | clinicalstudies@bicycletx.com |
United States, Florida | |
Florida Cancer Specialists | Recruiting |
Sarasota, Florida, United States, 34232 | |
Contact: Judy Wang, MD | |
United States, Oklahoma | |
Stephenson Cancer Center (Oklahoma University) | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact: Raid Aljumaily, MD | |
United States, Pennsylvania | |
Sidney Kimmel Cancer Center at Thomas Jefferson University | Recruiting |
Philadelphia, Pennsylvania, United States, 19107 | |
Contact: Babar Bashir, MD | |
United States, Tennessee | |
Tennessee Oncology, PLLC | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Contact: Johanna Bendell, MD | |
United Kingdom | |
Sarah Cannon Research Institute UK | Recruiting |
London, United Kingdom, W1G 6AD | |
Contact: Hendrik-Tobias Arkenau, MD |
Study Chair: | Johanna Bendell | Tennessee Oncology |
Responsible Party: | Bicycle Tx Limited |
ClinicalTrials.gov Identifier: | NCT04180371 |
Other Study ID Numbers: |
BT5528-100 |
First Posted: | November 27, 2019 Key Record Dates |
Last Update Posted: | January 20, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
EphA2 |
Neoplasms Nivolumab Antineoplastic Agents, Immunological Antineoplastic Agents |