The primary purpose of this expanded access program is to evaluate safety andtolerability of enfortumab vedotin (EV) in participants in the United States with locallyadvanced or metastatic urothelial carcinoma (UC) who have exhausted standard of caretherapies and are not eligible to participate in an ongoing EV clinical study. Thisprogram will also evaluate the efficacy of EV.
This treatment protocol is being conducted while a phase 3 enfortumab vedotin (EV) study
is ongoing for participants with previously treated locally advanced or metastatic
urothelial carcinoma (UC).
This is an expanded access program to provide EV to participants with locally advanced or
metastatic UC who have previously been treated with a programmed cell death protein 1
(PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum containing regimen
and for whom, in the judgment of the investigator, there is no available standard of care
therapy. The participants must not be eligible for an ongoing EV clinical study.
Participants who have previously participated in any EV studies or studies that included
EV as one of the treatment options are not eligible, even if the participants was not
given or assigned EV. To request enrollment, the investigator or designee will submit the
candidate participant's relevant medical history and other records in order to support
the participant's protocol eligibility.
Safety of EV will be assessed through evaluation of adverse events (AEs), serious adverse
events (SAEs), Eastern Cooperative Oncology Group (ECOG) performance status, laboratory
measurements, vital signs and physical examinations.
Participants will be provided with study medication until FDA approval and commercial
availability of enfortumab vedotin (EV) or termination by the sponsor.
Drug: enfortumab vedotin (EV)
Participants will receive an intravenously (IV) administered dose once weekly for the
first 3 weeks of every 4-week cycle (i.e., on days 1, 8, and 15)
Other Name: ASG-22CE
Inclusion Criteria:
- Subject has locally advanced or metastatic urothelial carcinoma (UC) and has
progressed during or after the most recent therapy.
- Subject has previously received a platinum containing regimen (i.e., cisplatin or
carboplatin) in the metastatic/locally advanced or neoadjuvant/adjuvant setting.
- If the platinum containing regimen was administered in the adjuvant/neoadjuvant
setting, progression on or after this treatment must be ≤ 12 months after
treatment completion.
- Subject has previously received treatment with a programmed cell death protein 1
(PD-1) inhibitor or programmed death-ligand 1 (PD-L1) inhibitor (including, but not
limited to, atezolizumab, pembrolizumab, durvalumab, avelumab and nivolumab) in the
metastatic/locally advanced setting.
- Subject treated with a PD-1 or PD-L1 inhibitor in the neoadjuvant/adjuvant
setting and had recurrent or progressive disease either during therapy or ≤ 3
months of therapy completion may be enrolled.
- Subject has exhausted available standard of care therapies for locally advanced or
metastatic UC.
- Subject may have had any number of prior lines of therapy for locally advanced
or metastatic UC.
- Subject has the following baseline laboratory data:
- absolute neutrophil count ≥ 1500/mm3
- platelet count ≥ 75 x 109/L
- hemoglobin ≥ 8 g/dL
- serum bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for subjects
with Gilbert's disease
- creatinine clearance (CrCl) ≥ 15 mL/min or ≥ 30 mL/min for subjects with
Eastern Cooperative Oncology Group (ECOG) performance status of 2 as estimated
per institutional standards or as measured by 24 hour urine collection
(glomerular filtration rate can also be used instead of CrCl)
- alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x ULN or ≤ 3 x
ULN for subjects with liver metastases
- Subject has ECOG performance status of 0, 1 or 2.
- Female subject is not pregnant and at least 1of the following conditions apply:
- not a woman of childbearing potential (WOCBP), or
- a WOCBP who agrees to follow the contraceptive guidance from the time of
informed consent through at least 6 months after final protocol treatment
administration.
- Female subject must agree not to breastfeed starting at screening and throughout the
treatment protocol period and for 6 months after final protocol treatment
administration.
- Female subject must not donate ova starting at first dose of investigational product
(IP) and throughout the treatment protocol period and for 6 months after final
protocol treatment administration.
- Male subject with female partner(s) of childbearing potential (including
breastfeeding partner) must agree to use contraception throughout the treatment
period and for 6 months after final protocol treatment administration.
- Male subject must not donate sperm during the treatment period and for 6 months
after final protocol treatment administration.
- Male subject with pregnant partner(s) must agree to remain abstinent or use a condom
for the duration of the pregnancy throughout the treatment protocol period and for 6
months after final protocol treatment administration.
- Subject agrees not to participate in another interventional study while receiving
treatment in the present treatment protocol.
Exclusion Criteria:
- Subject has ongoing sensory or motor neuropathy grade ≥ 2.
- Subject has ongoing clinically significant toxicity (grade 2 or higher with the
exception of alopecia) associated with prior treatment (including systemic therapy,
radiotherapy or surgery). Subject with hypothyroidism or panhypopituitarism related
to treatment with PD-1 and PD-L1 inhibitors may be enrolled. Subject on hormone
replacement therapy may be enrolled if on a stable dose.
- Subject has ongoing immunotherapy related myocarditis, colitis, uveitis or
pneumonitis or other immunotherapy related toxicities requiring high doses of
steroids (> 20 mg/day of prednisone or equivalent).
- Subject has previously received EV or enrolled in an EV study or a study that
included EV as one of the treatment options (even if the subject was not given EV).
- Subject is a candidate for any ongoing EV clinical studies.
- Subject has known hypersensitivity to EV or to any excipient contained in the drug
formulation of EV.
- Subject completed radiotherapy, major surgery or prior anticancer therapy ≤ 2 weeks
before first EV dose.
- Subject has history of uncontrolled diabetes mellitus ≤ 3 months of the first EV
dose. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c
between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that
are not otherwise explained.
- Subject is currently receiving systemic antimicrobial treatment for viral, bacterial
or fungal infection at the time of first dose of EV. Routine antimicrobial
prophylaxis is permitted.
- Subject has recent history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction or cardiac symptoms
(including congestive heart failure) consistent with New York Heart Association
Classes III to IV that is not adequately treated and/or controlled at the time of
first EV dose.
- Subject has other underlying medical condition that would impair the ability of the
subject to receive or tolerate EV.
UCLA Hematology Oncology
Los Angeles, California, United States
John Wayne Cancer Institute
Santa Monica, California, United States
St. Joseph Heritage Medical Group
Santa Rosa, California, United States
Holy Cross Hospital
Fort Lauderdale, Florida, United States
Cancer Specialists of North Florida
Jacksonville, Florida, United States
Northwestern University Medical Center
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Community Hospital Anderson
Anderson, Indiana, United States
New England Cancer Specialists
Topsham, Maine, United States
Johns Hopkins University
Baltimore, Maryland, United States
NYU Langone Health
New York, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Inova Schar Cancer Institute
Fairfax, Virginia, United States
Medical Director, Study Director
Astellas Pharma Global Development, Inc.