Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression
- Conditions
- Triple Negative Breast CancerUrothelial CancerOvarian CancerNon-small Cell Lung CancerAdvanced Solid Tumor Historically Known for High EphA2 ExpressionHead and Neck CancerGastric/Upper Gastrointestinal Cancer
- Interventions
- Registration Number
- NCT04180371
- Lead Sponsor
- BicycleTx Limited
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 288
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase I - Dose escalation combination (BT5528 & nivolumab) BT5528 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. Phase II - Dose expansion 1 (BT5528) 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 Phase I - Dose escalation (BT5528) 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. Phase I - Dose escalation combination (BT5528 & nivolumab) 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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
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 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 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
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 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 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
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 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 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
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 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 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
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 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) 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
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 Objective Response Rate (ORR)
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 Duration of Response (DOR)
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 Clinical benefit rate (CBR)
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 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)
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 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)
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 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 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 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)
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 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
All parts: Determine the plasma concentrations of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab 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 plasma concentrations of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
All parts: Determine the plasma concentrations of MMAE in plasma from all participants taking BT5528 alone and in combination with nivolumab 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 plasma concentrations of MMAE in plasma from all participants taking BT5528 alone and in combination with nivolumab
All parts: Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT5528 alone and in combination with nivolumab 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
Trial Locations
- Locations (32)
Sarah Cannon and HCA Research Institute
🇺🇸Nashville, Tennessee, United States
California Cancer Associates for Research and Excellence, Inc.
🇺🇸Encinitas, California, United States
University of California, San Diego (UCSD) - Medical Center
🇺🇸La Jolla, 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
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, 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
Women and Infants Hospital
🇺🇸Providence, Rhode Island, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Institut Jules Bordet
🇧🇪Brussels, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Antwerp University Hospital (UZA)
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent (UZ)
🇧🇪Gent, Belgium
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
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
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
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Sir Bobby Robson Cancer Trials Research Centre, The Northern Center for Cancer Care, Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom