A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)

• Register: ClinicalTrials.gov
• Last refreshed on: 8 April 2024
• Main ID: NCT03474107
• Date of registration: 16/03/2018
• Prospective Registration: Yes
• Primary sponsor: Astellas Pharma Global Development, Inc.
• Public title: A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
• Scientific title: An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
• Date of first enrolment: June 27, 2018
• Target sample size: 608
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03474107
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Canada, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Russian Federation, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Astellas Pharma Global Development, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject is legally an adult according to local regulation at the time of signing
informed consent.

- Subject has histologically or cytologically confirmed urothelial carcinoma (i.e.,
cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with urothelial
carcinoma (transitional cell) with squamous differentiation or mixed cell types are
eligible.

- Subject must have experienced radiographic progression or relapse during or after a
checkpoint inhibitor (CPI) (anti-programmed cell death protein 1 (PD1) or
anti-programmed death-ligand 1 (PD-L1)) for locally advanced or metastatic disease.
Subjects who discontinued CPI treatment due to toxicity are eligible provided that the
subjects have evidence of disease progression following discontinuation. The CPI need
not be the most recent therapy. Subjects for whom the most recent therapy has been a
non-CPI based regimen are eligible if the subjects have progressed/relapsed during or
after the subjects most recent therapy. Locally advanced disease must not be amenable
to resection with curative intent per the treating physician.

- Subject must have received a platinum containing regimen (cisplatin or carboplatin) in
the metastatic/locally advanced, neoadjuvant or adjuvant setting. If platinum was
administered in the adjuvant/neoadjuvant setting subject must have progressed within
12 months of completion.

- Subject has radiologically documented metastatic or locally advanced disease at
baseline.

- An archival tumor tissue sample should be available for submission to central
laboratory prior to study treatment. If an archival tumor tissue sample is not
available, a fresh tissue sample should be provided. If a fresh tissue sample cannot
be provided due to safety concerns, enrollment into the study must be discussed with
the medical monitor.

- Subject has ECOG PS of 0 or 1

- The subject has the following baseline laboratory data:

- absolute neutrophil count (ANC) = 1500/mm3

- platelet count = 100 × 10^9/L

- hemoglobin = 9 g/dL

- serum total bilirubin = 1.5 × upper limit of normal (ULN) or = 3 × ULN for
subjects with Gilbert's disease

- creatinine clearance (CrCl) = 30 mL/min as estimated per institutional standards
or as measured by 24 hour urine collection (glomerular filtration rate [GFR] can
also be used instead of CrCl)

- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN
or = 3 x ULN for subjects with liver metastases

- Female subject must either:

- Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year
without any menses for which there is no other obvious pathological or
physiological cause) prior to screening, or documented surgically sterile (e.g.,
hysterectomy, bilateral salpingectomy, bilateral oophorectomy).

- Or, if of childbearing potential: Agree not to try to become pregnant during the
study and for at least 6 months after the final study drug administration, and
have a negative urine or serum pregnancy test within 7 days prior to Day 1
(Females with false positive results and documented verification of negative
pregnancy status are eligible for participation), and if heterosexually active,
agree to consistently use a condom plus 1 form of highly effective birth control
per locally accepted standards starting at screening and throughout the study
period and for at least 6 months after the final study drug administration.

- Female subject must agree not to breastfeed or donate ova starting at screening and
throughout the study period, and for at least 6 months after the final study drug
administration.

- A sexually active male subject with female partner(s) who is of childbearing potential
is eligible if:

- Agrees to use a male condom starting at screening and continue throughout the
study treatment and for at least 6 months after final study drug administration.
If the male subject has not had a vasectomy or is not sterile as defined below
the subjects female partner(s) is utilizing 1 form of highly effective birth
control per locally accepted standards starting at screening and continue
throughout study treatment and for at least 6 months after the male subject
receives final study drug administration.

- Male subject must not donate sperm starting at screening and throughout the study
period, and for at least 6 months after the final study drug administration.

- Male subject with a pregnant or breastfeeding partner(s) must agree to abstinence or
use a condom for the duration of the pregnancy or time partner is breastfeeding
throughout the study period and for at least 6 months after the final study drug
administration.

- Subject agrees not to participate in another interventional study while on treatment
in present study.

Inclusion Criteria for COE:

- Subject is eligible for the COE if they continue to meet all inclusion criteria from
the main protocol in addition to the following when the patient is evaluated for
eligibility to participate in the COE portion of the study:

- Institutional review board (IRB)/ independent ethics committee (IEC) approved written
COE informed consent and privacy language as per national regulations (e.g., health
insurance portability and accountability act [HIPAA] Authorization for US sites) must
be obtained from the subject prior to any study-related procedures (including
withdrawal of prohibited medication, if applicable).

- Subject was randomized to Arm B and is either currently on study treatment or has
discontinued study treatment due to intolerance, AE or progression of disease and has
not started a new systemic anticancer treatment.

Exclusion Criteria:

- Subject has preexisting sensory or motor neuropathy Grade = 2.

- Subject has active central nervous system (CNS) metastases. Subjects with treated CNS
metastases are permitted on study if all the following are true:

- CNS metastases have been clinically stable for at least 6 weeks prior to
screening

- If requiring steroid treatment for CNS metastases, the subject is on a stable
dose = 20 mg/day of prednisone or equivalent for at least 2 weeks

- Baseline scans show no evidence of new or enlarged brain metastasis




Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Ureteral Cancer

Bladder Cancer

Urothelial Cancer

Intervention(s)

Drug: Paclitaxel

Drug: Vinflunine

Drug: Docetaxel

Drug: Enfortumab Vedotin

Primary Outcome(s)

Overall Survival (OS) [Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)]

Secondary Outcome(s)

Disease Control Rate (DCR) as Per RECIST V1.1 [Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)]

Duration of Response (DOR) as Per RECIST V1.1 [Time Frame: From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)]

Change From Baseline to Week 12 in European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Global Health Status (QL2 Score) [Time Frame: Baseline and week 12]

Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)]

Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS) [Time Frame: Baseline and week 12]

Overall Response Rate (ORR) as Per RECIST V1.1 [Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)]

Number of Participants With ECOG Performance Status [Time Frame: End of treatment (EOT) (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)]

Number of Participants With Treatment Emergent Adverse Events [Time Frame: From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)]

Secondary ID(s)

2017-003344-21

7465-CL-0301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Seagen Inc.

Results

• Results available: Yes
• Date Posted: 24/08/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03474107