Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Malignancies
- Conditions
- Urinary Bladder NeoplasmTriple Negative Breast NeoplasmsHormone Receptor Positive, HER2-negative NeoplasmsHormone Receptor Positive, HER2-low NeoplasmsBreast NeoplasmsNon-Small-Cell Lung NeoplasmsOvarian NeoplasmAdvanced Solid Tumor
- Interventions
- Registration Number
- NCT04561362
- Lead Sponsor
- BicycleTx Limited
- Brief Summary
This study is a Phase I/II, multicenter, first-in-human, open-label dose-escalation study of BT8009 given as a single agent and in combination with pembrolizumab in participants with advanced solid tumors associated with Nectin-4 expression or in participants with advanced solid tumor malignancies having renal insufficiency. The primary endpoints are: Dose limiting toxicities (Parts A-1 and A-2), Overall response rate per RECIST v1.1 (Part B), Safety and tolerability (Part C), and characterization of the pharmacokinetics (Part D).
- Detailed Description
This study will assess the safety and tolerability of BT8009 alone and in combination with pembrolizumab in patients with select advanced solid tumors. BT8009 will be given as a single agent in 3 different dosing schedules- weekly (28 day cycle), biweekly (28 day cycle) or dosing on day 1 and day 8 of a 3-weekly (21 day cycle) and in combination with pembrolizumab. There are three parts to this study. Part A is a dose escalation in patients with select advanced solid tumors primarily designed to evaluate safety and tolerability of BT8009 as monotherapy or in combination with pembrolizumab and to determine a recommended Phase II dose (RP2D). Following a selection of an RP2D, Part B, a dose expansion portion, will be initiated with the primary objective of clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab in patients with select advanced solid tumors. Part C will evaluate safety and tolerability of RP2D in patients with renal insufficiency. Part D will further characterize the pharmacokinetics of BT8009 and MMAE.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 329
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion BT8009 Participants will receive a selected dose of BT8009 and standard dose of pembrolizumab. Part D - BT8009 Monotherapy Supplementary PK BT8009 Participants will receive a selected dose of BT8009. Cohort B-1 - BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Cohort B-2- BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Cohort B-3- BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. . Cohort B-5- BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Cohort B-6- BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Part C - Renal Insufficiency BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Part B-9 - BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Part A-1 -BT8009 Monotherapy Dose Escalation BT8009 Participants will receive escalating doses of BT8009 via IV. Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort B-4- BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Part B-8 - BT8009 Monotherapy Dose Expansion BT8009 Participants will receive a selected dose of BT8009. Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion Pembrolizumab Participants will receive a selected dose of BT8009 and standard dose of pembrolizumab.
- Primary Outcome Measures
Name Time Method Parts A-1, A-2 and C: Number of participants with treatment emergent adverse events, receiving BT8009 as a monotherapy or in combination with pembrolizumab to assess safety and tolerability. From cycle 1 day 1 until 30 days after the end of treatment or approximately 1 year Safety reported as incidence of treatment-emergent adverse events using CTCAE v5.0 criteria.
Parts A-1 and A-2 (escalations): Number of participants with dose limiting toxicities on BT8009 as a monotherapy or in combination with pembrolizumab 28 days (for cycles that are either 21 or 28 days in length depending on dosing schedule assigned) Number of patients who experience dose limiting toxicities BT8009 when given as a monotherapy or in combination with pembrolizumab.
Part B1-B7: Objective response rate (ORR) to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab using RECIST 1.1. Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or, death, or up to three years Proportion of participants with confirmed complete response or partial response to BT8009 as a monotherapy or in combination with pembrolizumab according to RECIST 1.1 criteria.
Part D: Maximum plasma concentration (Cmax) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy From Cycle 1 Day 1 through end of treatment or for up to 1 year Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone.
Part D: Minimum plasma concentration (Cmin) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy From Cycle 1 Day 1 through end of treatment or for up to 1 year Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone
Part D: Area under the plasma concentration-time curve (AUC) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy From Cycle 1 Day 1 through end of treatment or for up to 1 year Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone.
Part D: Elimination half-life (t1/2) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy From Cycle 1 Day 1 through end of treatment or for up to 1 year Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone.
PartsB-8, B-9: Number of participants with treatment emergent adverse events receiving an alternative dosing regimen of BT8009 monotherapy to assess safety and tolerability. From cycle 1 day 1 until at least 30 days after the end of treatment (each cycle is 21 days) Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving an alternative dose regimen of BT8009 as a monotherapy who experience treatment-emergent adverse events using CTCAE v5.0 criteria.
- Secondary Outcome Measures
Name Time Method Parts B-1-B-7: Number of participants with treatment emergent adverse events receiving BT8009 as a monotherapy or in combination with pembrolizumab to assess safety and tolerability. From cycle 1 day 1 until at least 30 days after the end of treatment (each cycle is 21 or 28 days depending on the assigned dosing schedule) Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving BT8009 as a monotherapy or in combination with pembrolizumab who experience treatment-emergent adverse events using CTCAE v5.0 criteria.
Part B: Duration of Response time to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or, death, or up to three years Duration of objective response (complete or partial response) by RECIST 1.1 in participants receiving BT8009 as a monotherapy or in combination with pembrolizumab
Part B: Clinical benefit rate to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to 3 years Proportion of participants who have complete response (CR), partial response (PR), or stable disease (SD) for at least 16 weeks according to RECIST Version 1.1 criteria.
Part B: Progression-free survival time to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab. Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years The time from the first day of study drug administration (Day 1) to disease progression according to RECIST 1.1 criteria in participants receiving BT8009 as a monotherapy or in combination with pembrolizumab.
Part B: Overall survival time to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab using RECIST 1.1 Every 8 weeks for the first 12 months then every 12 weeks until death, then every 3 months for up to 1 year after last patient accrued The time from start of study drug administration (Day 1) until death due to any cause in participants receiving BT8009 as a monotherapy or in combination with pembrolizumab.
Cohorts B-4, B-5, and B-6: Objective response rate by Nectin-4 status of BT8009 as a monotherapy in patients with selected solid tumor using RECIST 1.1. Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years Proportion of participants with confirmed complete response or partial response to BT8009 as a monotherapy according to RECIST 1.1 criteria categorized by Nectin-4 expression status.
Parts A-1, A-2, B-8, B-9, and C: Objective response rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab. Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death or up to three years Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency with confirmed complete response or partial response according to RECIST 1.1 criteria
Parts A-1, A-2, C and D: Duration of Response time to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab. Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death or up to three years Duration of objective response (complete or partial response) by RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as a monotherapy or in combination with pembrolizumab.
Parts A-1, A-2, C and D: Clinical benefit rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab Every 8 weeks for the first 12 months then every 12 weeks until disease progression for up to 3 years Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency who have complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks according to the RECIST Version 1.1 criteria.
Parts A-1, A-2, C and D: Progression-free survival time (months) to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years The time from start of study drug administration until disease progression according to RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as a monotherapy or in combination with pembrolizumab.
Parts A-1, A-2, C and D: Overall survival time (months) to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab. Every 8 weeks for the first 12 months then every 12 weeks until disease progression, then every 3 months for up to 1 year after last patient is accrued The time from start of study drug administration until death due to any cause in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as a monotherapy or in combination with pembrolizumab.
Part A, B and C: Maximum plasma concentration (Cmax) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.
Part A, B and C: Minimum plasma concentration (Cmin) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.
Part A, B and C: Area under the plasma concentration-time curve (AUC) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.
Part A, B and C: Elimination half-life (t1/2) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.
Part C: Maximum plasma concentration (Cmax) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.
Part C: Minimum plasma concentration (Cmin) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherap. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.
Part C: Area under the plasma concentration-time curve (AUC) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.
Part C: Elimination half-life (t1/2) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy. From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.
All cohorts: Number of participants positive for anti-drug antibodies (ADA) to determine incidence of ADA From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule) Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT8009 as a monotherapy or in combination with pembrolizumab
Part D: Number of participants with treatment emergent adverse events receiving BT8009 as a monotherapy to assess safety and tolerability in participants with normal renal function or mild renal insufficiency. From cycle 1 day 1 until at least 30 days after the end of treatment Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving BT8009 with normal renal function or mild renal insufficiency who experience treatment-emergent adverse events using CTCAE v5.0 criteria.
Trial Locations
- Locations (29)
Centre Eugene Marquis
🇫🇷Rennes, France
Institut Bergonie
🇫🇷Bordeaux, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Next Oncology - Hospital Quironsalud Madrid
🇪🇸Pozuelo de Alarcon, Spain
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, MI, Italy
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Mary Crowley Cancer Research Center
🇺🇸Dallas, Texas, United States
University Health Network, Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Horizon Oncology Research
🇺🇸Lafayette, Indiana, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
START Madrid Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Ospedale San Raffaele
🇮🇹Milan, Italy
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Norton Cancer Institute, Downtown
🇺🇸Louisville, Kentucky, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Advent Health
🇺🇸Orlando, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States