Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06439836
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-05-31
Brief Title:
Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 1 Trial of CA-4948 in Combination With Pembrolizumab to Overcome Resistance to PD-1PD-L1 Blockade in Metastatic Urothelial Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
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 I trial tests the safety side effects best dose and effectiveness of emavusertib CA-4948 in combination with pembrolizumab in treating patients with urothelial cancer that has spread from where it first started to other places in the body metastatic and that has a resistance to PD-1PD-L1 immune checkpoint inhibitors CA-4948 a kinase inhibitor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Immunotherapy with monoclonal antibodies such as pembrolizumab may help the bodys immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread Giving CA-4948 in combination with pembrolizumab may be safe tolerable andor effective in treating patients with metastatic urothelial cancer that is resistant to PD-1PD-L1 immune checkpoint inhibitors
Detailed Description:
PRIMARY OBJECTIVES
I To determine the recommended phase 2 dose of the combination of CA-4948 plus pembrolizumab in patients with immune checkpoint blockade ICB-resistant metastatic urothelial cancer Dose Escalation Cohort
II To determine the safety of the combination of CA-4948 plus pembrolizumab in patients with ICB-resistant metastatic urothelial cancer Dose Escalation Cohort and Dose Expansion Cohort
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To measure the objective response complete response CR or partial response PR as defined by Response Evaluation Criteria in Solid Tumors RECIST 11 at 9 weeks and the best overall response CR or PR as defined by RECIST 11 at any time while on study
III To determine progression-free survival overall survival and duration of response
IV To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in 2IR scores as defined by ribonucleic acid RNA sequencing in paired tumor biopsies
EXPLORATORY OBJECTIVES
I To assess the clinical benefit rate with pembrolizumab plus CA-4948 therapy II To assess the C-reactive protein CRP response rate as defined by the proportion of patients achieving a 15 fold reduction in CRP at 9 weeks
III To explore the association between the 2IR score as defined by bulk-ribonucleic acid RNA sequencing of pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
IV To explore whether CA-4948 plus pembrolizumab leads to on-treatment changes in the cellular andor molecular composition of the tumor microenvironment TME
V To explore the association between the quantity and spatial localization of SPP1 monocytes-macrophages MoMacs defined by multiplex immunohistochemistry on pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
VI To explore the association between the cellular and molecular composition of the TME defined by spatial RNA sequencing on pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
VII To explore on-treatment changes in high-sensitivity hs CRP and cytokines and chemokines in peripheral blood and their association with objective response rate clinical benefit rate progression-free survival andor overall survival
VIII To explore the association between PD-L1 expression on pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
IX To explore the association between the CXCL9SPP1 ratio as defined by bulk-RNA sequencing of pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
X To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in the CXCL9SPP1 ratio as defined by RNA sequencing in paired tumor biopsies
OUTLINE This is a dose-escalation study of CA-4948 in combination with pembrolizumab followed by a dose-expansion study
Patients receive CA-4948 orally PO twice daily BID on days 1-21 and pembrolizumab intravenously IV over 30 minutes on day 1 of each cycle Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity Patients undergo blood sample collection computed tomography CT magnetic resonance imaging MRI or positron emission tomography PET throughout the study Additionally patients may undergo a tumor biopsy on study
After completion of study treatment patients are followed up every 3 months for 2 years
I To determine the recommended phase 2 dose of the combination of CA-4948 plus pembrolizumab in patients with immune checkpoint blockade ICB-resistant metastatic urothelial cancer Dose Escalation Cohort
II To determine the safety of the combination of CA-4948 plus pembrolizumab in patients with ICB-resistant metastatic urothelial cancer Dose Escalation Cohort and Dose Expansion Cohort
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To measure the objective response complete response CR or partial response PR as defined by Response Evaluation Criteria in Solid Tumors RECIST 11 at 9 weeks and the best overall response CR or PR as defined by RECIST 11 at any time while on study
III To determine progression-free survival overall survival and duration of response
IV To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in 2IR scores as defined by ribonucleic acid RNA sequencing in paired tumor biopsies
EXPLORATORY OBJECTIVES
I To assess the clinical benefit rate with pembrolizumab plus CA-4948 therapy II To assess the C-reactive protein CRP response rate as defined by the proportion of patients achieving a 15 fold reduction in CRP at 9 weeks
III To explore the association between the 2IR score as defined by bulk-ribonucleic acid RNA sequencing of pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
IV To explore whether CA-4948 plus pembrolizumab leads to on-treatment changes in the cellular andor molecular composition of the tumor microenvironment TME
V To explore the association between the quantity and spatial localization of SPP1 monocytes-macrophages MoMacs defined by multiplex immunohistochemistry on pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
VI To explore the association between the cellular and molecular composition of the TME defined by spatial RNA sequencing on pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
VII To explore on-treatment changes in high-sensitivity hs CRP and cytokines and chemokines in peripheral blood and their association with objective response rate clinical benefit rate progression-free survival andor overall survival
VIII To explore the association between PD-L1 expression on pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
IX To explore the association between the CXCL9SPP1 ratio as defined by bulk-RNA sequencing of pre-treatment tumor tissue and objective response rate clinical benefit rate progression-free survival andor overall survival
X To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in the CXCL9SPP1 ratio as defined by RNA sequencing in paired tumor biopsies
OUTLINE This is a dose-escalation study of CA-4948 in combination with pembrolizumab followed by a dose-expansion study
Patients receive CA-4948 orally PO twice daily BID on days 1-21 and pembrolizumab intravenously IV over 30 minutes on day 1 of each cycle Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity Patients undergo blood sample collection computed tomography CT magnetic resonance imaging MRI or positron emission tomography PET throughout the study Additionally patients may undergo a tumor biopsy on study
After completion of study treatment patients are followed up every 3 months for 2 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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 10636 | OTHER | CTEP | None |
| NCI-2024-04436 | REGISTRY | None | None |
| 10636 | OTHER | None | None |