Trial Title:
Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology
NCT ID:
NCT05756569
Condition:
Bladder Squamous Cell Carcinoma
Locally Advanced Bladder Carcinoma
Malignant Renal Pelvis Neoplasm
Malignant Ureter Neoplasm
Malignant Urethral Neoplasm
Metastatic Bladder Carcinoma
Stage III Bladder Cancer AJCC v8
Stage IV Bladder Cancer AJCC v8
Unresectable Bladder Carcinoma
Urachal Adenocarcinoma
Bladder Adenocarcinoma
Conditions: Official terms:
Carcinoma
Neoplasms
Adenocarcinoma
Urinary Bladder Neoplasms
Urethral Neoplasms
Pelvic Neoplasms
Ureteral Neoplasms
Pembrolizumab
Immunoconjugates
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood
Arm group label:
Treatment (enfortumab vedotin, pembrolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (enfortumab vedotin, pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Enfortumab Vedotin
Description:
Given IV
Arm group label:
Treatment (enfortumab vedotin, pembrolizumab)
Other name:
AGS 22ME
Other name:
AGS-22M6E
Other name:
Anti-Nectin 4 ADC ASG-22CE
Other name:
Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E
Other name:
ASG-22CE
Other name:
Enfortumab Vedotin-ejfv
Other name:
Padcev
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (enfortumab vedotin, pembrolizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (enfortumab vedotin, pembrolizumab)
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
SCH 900475
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (enfortumab vedotin, pembrolizumab)
Summary:
This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in
treating patients with bladder cancer of variant histology (a group of less common types
of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or
that has spread from where it first started (primary site) to other places in the body
(metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an
anticancer drug called vedotin. 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. Immunotherapy with monoclonal antibodies, such as pembrolizumab,
may help the body's immune system attack the cancer, and may interfere with the ability
of tumor cells to grow and spread. Giving enfortumab vedotin and pembrolizumab may kill
more tumor cells in patients with locally advanced or metastatic bladder cancer of
variant histology.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the anti-tumor activity of the combination of enfortumab vedotin (EV) plus
pembrolizumab by assessing the overall response rate (ORR) as measured by Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1.
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of the combination as measured by progression free survival,
overall survival, and duration of response.
II. To evaluate the safety as measured by incidence of adverse events assessed up to 2
years.
EXPLORATORY OBJECTIVE:
I. To assess tissue-based assays in archival tissue and correlative changes in peripheral
T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and
cytokines.
OUTLINE:
Patients receive enfortumab vedotin intravenously (IV) and pembrolizumab IV on study.
Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI),
and collection of blood throughout the trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Male or Female
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Metastatic disease or unresectable locally advanced disease
- Histologically documented variant histology (nested, microcytic, micropapillary,
lymphoepithelioma-like, plasmacytoid, giant cell, poorly differentiated, lipid-rich,
clear cell, sarcomatoid) bladder cancer and non-urothelial bladder cancer of
epithelial origin including squamous cell carcinoma and adenocarcinoma (urachal and
non-urachal). Variant histology tumors and non-urothelial tumors of ureter, urethra,
urachus, or renal pelvis are included. Patients with mixed cell type are eligible if
the predominant histology (over 50%) is variant or non-urothelial. All histological
classifications will follow the 2016 WHO Classifications.
- Untreated or having received any number of lines of prior therapy
- Tumor tissue samples must be available for submission prior to initiation of study
treatment. If not, agree to undergo biopsy
- Patients must have measurable disease as defined by RECIST criteria 1.1 as at least
one lesion that can be accurately measured in at least one dimension (longest
diameter of >= 10 mm for non-nodal lesions or short axis of >= 15 mm for nodal
lesions) on CT scan, MRI
- Patients must have adequate organ and marrow function, within 28 days of cycle 1 day
1, at the discretion of the investigator
- The effects of study drugs on the developing human fetus are unknown. For this
reason, female of child-bearing potential (FCBP) must have a negative serum or urine
pregnancy test prior to starting therapy
- FCBP and men treated or enrolled on this protocol must agree to use adequate
contraception (hormonal or barrier method of birth control; or abstinence) prior to
study entry and for the duration of study participation. Additionally, FCBP and male
subjects should use effective contraception for 6 months after the last dose. Should
a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
Male subjects must not donate sperm and female subjects must not donate ova from
screening to 6 months after the last dose
- A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any time
in the preceding 24 consecutive months)
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy,
immunotherapy, or investigational therapy) for the treatment of cancer >= 4 weeks
before the start of study therapy
- Life expectancy > 12 weeks as determined by the Investigator
- Willingness and ability of the subject to comply with scheduled visits, drug
administration plan, protocol-specified laboratory tests, other study procedures,
and study restrictions
- Evidence of a personally signed informed consent indicating that the subject is
aware of the neoplastic nature of the disease and has been informed of the
procedures to be followed, the experimental nature of the therapy, alternatives,
potential risks and discomforts, potential benefits, and other pertinent aspects of
study participation
Exclusion Criteria:
- The neuroendocrine histology (small cell and large cell carcinomas) and
non-epithelial bladder tumors (e.g. bladder sarcoma, carcinosarcoma, paraganglioma,
melanoma, primary lymphoma, and lymphoepithelioma-like carcinoma) are excluded.
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier [i.e. ongoing clinically significant toxicity
(grade 2 or higher with the exception of alopecia) associated with prior treatment]
- Patients who are receiving any other investigational agents or an investigational
device within 21 days before administration of first dose of study drugs
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to the agents used in study
- Patients with ongoing sensory or motor neuropathy grade >= 2
- Prior treatment or enrollment in a study with EV or PD1/PD-L1 immune checkpoint
inhibitor (including maintenance therapy)
- Known uncontrolled diabetes mellitus with glycated hemoglobin (HbA1c) >= 8% or HbA1c
7% to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not
otherwise explained
- Active central nervous system (CNS) metastases
- Excluding the primary tumor leading to enrollment in this study, any other active
malignancy (except for localized prostate cancer, definitively treated melanoma
in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the
bladder or cervix) within the past 24 months
- Currently receiving systemic antimicrobial treatment for active infection or high
dose steroids (> 10mg of prednisone or equivalent)
- A FCBP who has a positive urine pregnancy test at baseline or within 72 hours prior
to receiving first study dose. If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required
- Breastfeeding females
- History of active autoimmune disease that has required systemic treatment in the
past 2 years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs), known hepatitis B (defined as hepatitis B surface antigen
[HBsAg] reactive), known active hepatitis C virus (defined as HCV ribonucleic acid
[mRNA] [qualitative] is detected) or tuberculosis
- History of active keratitis or corneal ulcerations
- History of allogenic tissue/solid organ transplant
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina
pectoris, serious cardiac arrhythmias within 6 months prior to first dose of
EV/pembrolizumab
- Other uncontrolled current illness including, but not limited to, cardiac arrhythmia
or psychiatric illness/social situations that would limit compliance with study
requirements
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Grady Health System
Address:
City:
Atlanta
Zip:
30303
Country:
United States
Status:
Recruiting
Contact:
Last name:
Wilena Session
Phone:
404-778-4005
Email:
wsessio@emory.edu
Investigator:
Last name:
Bassel Nazha, MD, MPH
Email:
Principal Investigator
Facility:
Name:
Emory University Hospital Midtown
Address:
City:
Atlanta
Zip:
30308
Country:
United States
Status:
Recruiting
Contact:
Last name:
Wilena Session
Phone:
404-778-4005
Email:
wsessio@emory.edu
Investigator:
Last name:
Bassel Nazha, MD, MPH
Email:
Principal Investigator
Facility:
Name:
Emory University Hospital/Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Wilena Session
Phone:
404-778-4005
Email:
wsessio@emory.edu
Investigator:
Last name:
Bassel Nazha, MD, MPH
Email:
Principal Investigator
Facility:
Name:
Emory Saint Joseph's Hospital
Address:
City:
Atlanta
Zip:
30342
Country:
United States
Status:
Recruiting
Contact:
Last name:
Wilena Session
Phone:
404-778-4005
Email:
wsessio@emory.edu
Investigator:
Last name:
Bassel Nazha, MD, MPH
Email:
Principal Investigator
Start date:
September 26, 2023
Completion date:
December 16, 2027
Lead sponsor:
Agency:
Emory University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Collaborator:
Agency:
Astellas Pharma Inc
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Emory University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05756569
