Metastatic Urothelial Carcinoma Clinical Trial
Official title:
Phase Ib Trial of Erdafitinib Combined With Enfortumab Vedotin Following Platinum and PD1/L1 Inhibitors for Metastatic Urothelial Carcinoma With FGFR2/3 Genetic Alterations
This phase Ib trial evaluates the best dose, potential benefits, and/or side effects of erdafitinib in combination with enfortumab vedotin in treating patients with bladder cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and possesses genetic alterations in FGFR2/3 genes. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. 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 cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Giving erdafitinib in combination with enfortumab vedotin may shrink or stabilize metastatic bladder cancer with alterations in FGFR 2/3 genes.
PRIMARY OBJECTIVES: I. To determine the feasibility and safety of erdafitinib when combined with enfortumab vedotin (EV) for patients with metastatic urothelial carcinoma (mUC) harboring FGFR2/3 activating genomic alterations who are progressing following platinum-based chemotherapy and PD1/L1 inhibitors. II. To determine the maximally tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of EV when combined with erdafitinib. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To observe and record overall response rate (ORR). III. To observe and record duration of response (DOR). IV. To observe and record progression-free survival (PFS). V. To observe and record overall survival (OS). EXPLORATORY OBJECTIVES: I. Assess association of tumor PD-L1 and nectin-4 protein expression with response. II. Use commercial tissue next generation sequencing (NGS) assay to confirm FGFR status as well as to describe the genomic landscape of metastatic UC. III. Use commercial liquid NGS assay to assess genomic changes by circulating tumor (ct)-deoxyribonucleic acid (DNA) assessment to study mechanisms of resistance with treatment. IV. Assess pharmacokinetic (PK) of monomethyl auristatin E (MMAE) and erdafitinib. OUTLINE: This is a dose-escalation study of enfortumab vedotin in combination with fixed dose erdafitinib followed by a dose-expansion study of the drug combination. Patients receive erdafitinib orally (PO) once daily (QD) on days 1-28 of each cycle and enfortumab vedotin intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and blood sample collection throughout the trial. After completion of study treatment, patients are followed up every 3 months for up to 2 years. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT05700344 -
SOGUG-AVELUMAB_RWD
|
||
| Recruiting |
NCT04623502 -
An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy
|
N/A | |
| Recruiting |
NCT05107674 -
A Study of NX-1607 in Adults With Advanced Malignancies
|
Phase 1 | |
| Recruiting |
NCT04953104 -
Nivolumab for the Treatment of Patients With Metastatic Urothelial Cancer With ARID1A Mutation and Stratify Response Based on CXCL13 Expression
|
Phase 2 | |
| Withdrawn |
NCT06050954 -
A Pilot Study of Circulating Tumor DNA Adaptive Risk Maintenance Approach for Bladder Cancer (CARMA)
|
Phase 2 | |
| Active, not recruiting |
NCT03534804 -
Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma
|
Phase 2 | |
| Active, not recruiting |
NCT00365157 -
Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
|
Phase 1/Phase 2 | |
| Withdrawn |
NCT06018116 -
A Canadian Trial of Bicalutamide in Patients Receiving Maintenance Avelumab for Metastatic Urothelial Cancer.
|
Phase 2 | |
| Recruiting |
NCT05544552 -
Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
|
Phase 1/Phase 2 | |
| Recruiting |
NCT04936230 -
Immunotherapy With or Without Radiation Therapy for Metastatic Urothelial Cancer
|
Phase 2 | |
| Active, not recruiting |
NCT04514484 -
Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV
|
Phase 1 | |
| Terminated |
NCT05052372 -
Biomarker Research Study for Patients With FGFR-Mutant Bladder Cancer Receiving Erdafitinib
|
||
| Terminated |
NCT03115801 -
A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers
|
Phase 2 | |
| Active, not recruiting |
NCT03854474 -
Testing the Addition of Tazemetostat to the Immunotherapy Drug, Pembrolizumab (MK-3475), in Advanced Urothelial Carcinoma
|
Phase 1/Phase 2 | |
| Terminated |
NCT02693717 -
Pemetrexed Disodium in Treating Patients With Previously Treated Metastatic Urothelial Cancer
|
Phase 2 | |
| Recruiting |
NCT04848519 -
Immune Checkpoint Inhibitors With or Without Propranolol Hydrochloride In Patients With Urothelial Carcinoma
|
Phase 2 | |
| Active, not recruiting |
NCT04724018 -
Sacituzumab Govitecan Plus EV in Metastatic UC
|
Phase 1 | |
| Terminated |
NCT04003610 -
Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)
|
Phase 2 | |
| Recruiting |
NCT04383067 -
A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients
|
Phase 2 | |
| Not yet recruiting |
NCT03108261 -
Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations
|
Phase 2 |