Ignite Creation Date:
2024-07-17 @ 10:50 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06470282
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-24
First Post:
2024-06-17
Brief Title:
Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Phase IbII Study of Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy as a Bladder-Sparing Trimodality Therapy in Muscle Invasive Bladder Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase IbII trial studies the side effects best dose and effectiveness of enfortumab vedotin EV in combination with pembrolizumab and radiation therapy for treating patients with muscle invasive bladder cancer Standard of care treatment for muscle invasive bladder cancer is chemotherapy to shrink the tumor before the main treatment is given neoadjuvant followed by surgery to remove all of the bladder as well as nearby tissues and organs radical cystectomy In cases where patients are not candidates for the standard of care approach or prefer a bladder sparing option tri-modality therapy with transurethral resection of bladder tumor TURBT followed by combined chemotherapy and radiation therapy is used Enfortumab vedotin is a monoclonal antibody enfortumab linked to an anticancer drug called vedotin It works by helping the immune system to slow or stop the growth of tumor cells Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them It is a type of antibody-drug conjugate Immunotherapy with monoclonal antibodies such as pembrolizumab may help the bodys immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor Thin beams of radiation of different intensities are aimed at the tumor from many angles This type of radiation therapy reduces the damage to healthy tissue near the tumor Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer
Detailed Description:
PRIMARY OBJECTIVES
I To determine the recommended phase II dose RP2D of enfortumab vedotin given in combination with pembrolizumab and concurrent radiation therapy RT Phase Ib
II To assess the toxicity and safety of enfortumab vedotin given in combination with pembrolizumab and concurrent radiation therapy RT Phase Ib
III To evaluate the rate of clinical complete response to treatment cCR at the RP2D based on 6-month post-treatment cystoscopy TURBT cytology and cross sectional imaging Phase II
IV To characterize the safety of enfortumab vedotin at the RP2D given in combination with pembrolizumab and concurrent radiation therapy RT Phase II
SECONDARY OBJECTIVES
I To evaluate the rate of cCR 6 months post-treatment start based on cystoscopy TURBT and cross sectional imaging Phase Ib II To evaluate the preliminary efficacy of enfortumab vedotin given in combination with pembrolizumab and concurrent radiation therapy RT as measured by 1-year recurrence free survival rate 2-year cystectomy-free survival rate 2-year overall survival rate the median recurrence free survival RFS rate median overall survival and median cystectomy-free survival Phase Ib and Phase II III To assess the downstaging to pT1N0 pT1 or less following completion of treatment based on 6-month post-treatment cystoscopy for participants treated at RP2D of enfortumab vedotin EV Phase Ib and Phase II IV To assess the downstaging to pT1N0 or less following completion of treatment based on 6-month post-treatment cystoscopy for participants across all EV dose levels Phase Ib and Phase II
EXPLORATORY OBJECTIVES
I Assessment of change in tumor gene expression signatures using single-cell ribonucleic acid RNA sequencing scRNA-Seq following initiation of combination treatment
II Assessment of the change in the populations of tumor-infiltrating immune cells TIICs induced by initiation of the combination treatment
III Determination of the impact of EVpembrolizumab combination treatment on programmed death-ligand 1 PD-L1 expression in tumor cells and TIICs as well as on other immunologic predictive markers
IV Assessment of modulation of tumor microenvironment pre- and post-initiation of combination treatment using multiplex immunohistochemistry IHC
V Assessment of the modulation of circulating immune cells following initiation of combination treatment using mass cytometry cytometry by time of flight or CyTOF
VI Assessment of the change in T-cell receptor repertoire by scRNA-Seq following initiation of combination treatment
VII Change in tumor expression of nectin cell adhesion molecule 4 Nectin-4 following combination treatment relative to baseline
VIII Assessment in the change in CD3 T cell density T cell countĪ¼m2 from baseline biopsy to post-RT biopsy in participants with residual tumor across all EV dose levels and at RP2D
OUTLINE
This is a phase Ib dose escalation study of enfortumab vedotin followed by a phase II study
Participants receive enfortumab vedotin and pembrolizumab for up to 5 cycle of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity Beginning on cycle 1 day 1 participants also undergo non-investigational standard of care intensity modulated radiation therapy IMRT over 65-8 weeks
After completion of study treatment participants are followed up at 90 days and then every 12 weeks for up to 5 years
I To determine the recommended phase II dose RP2D of enfortumab vedotin given in combination with pembrolizumab and concurrent radiation therapy RT Phase Ib
II To assess the toxicity and safety of enfortumab vedotin given in combination with pembrolizumab and concurrent radiation therapy RT Phase Ib
III To evaluate the rate of clinical complete response to treatment cCR at the RP2D based on 6-month post-treatment cystoscopy TURBT cytology and cross sectional imaging Phase II
IV To characterize the safety of enfortumab vedotin at the RP2D given in combination with pembrolizumab and concurrent radiation therapy RT Phase II
SECONDARY OBJECTIVES
I To evaluate the rate of cCR 6 months post-treatment start based on cystoscopy TURBT and cross sectional imaging Phase Ib II To evaluate the preliminary efficacy of enfortumab vedotin given in combination with pembrolizumab and concurrent radiation therapy RT as measured by 1-year recurrence free survival rate 2-year cystectomy-free survival rate 2-year overall survival rate the median recurrence free survival RFS rate median overall survival and median cystectomy-free survival Phase Ib and Phase II III To assess the downstaging to pT1N0 pT1 or less following completion of treatment based on 6-month post-treatment cystoscopy for participants treated at RP2D of enfortumab vedotin EV Phase Ib and Phase II IV To assess the downstaging to pT1N0 or less following completion of treatment based on 6-month post-treatment cystoscopy for participants across all EV dose levels Phase Ib and Phase II
EXPLORATORY OBJECTIVES
I Assessment of change in tumor gene expression signatures using single-cell ribonucleic acid RNA sequencing scRNA-Seq following initiation of combination treatment
II Assessment of the change in the populations of tumor-infiltrating immune cells TIICs induced by initiation of the combination treatment
III Determination of the impact of EVpembrolizumab combination treatment on programmed death-ligand 1 PD-L1 expression in tumor cells and TIICs as well as on other immunologic predictive markers
IV Assessment of modulation of tumor microenvironment pre- and post-initiation of combination treatment using multiplex immunohistochemistry IHC
V Assessment of the modulation of circulating immune cells following initiation of combination treatment using mass cytometry cytometry by time of flight or CyTOF
VI Assessment of the change in T-cell receptor repertoire by scRNA-Seq following initiation of combination treatment
VII Change in tumor expression of nectin cell adhesion molecule 4 Nectin-4 following combination treatment relative to baseline
VIII Assessment in the change in CD3 T cell density T cell countĪ¼m2 from baseline biopsy to post-RT biopsy in participants with residual tumor across all EV dose levels and at RP2D
OUTLINE
This is a phase Ib dose escalation study of enfortumab vedotin followed by a phase II study
Participants receive enfortumab vedotin and pembrolizumab for up to 5 cycle of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity Beginning on cycle 1 day 1 participants also undergo non-investigational standard of care intensity modulated radiation therapy IMRT over 65-8 weeks
After completion of study treatment participants are followed up at 90 days and then every 12 weeks for up to 5 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-04701 | REGISTRY | None | None |