Clinical Trials /

Enfortumab Vedotin and Pembrolizumab, With or Without Chemotherapy, vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

NCT04223856

Description:

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together alone or with platinum chemotherapy to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Enfortumab Vedotin and Pembrolizumab, With or Without Chemotherapy, vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer
  • Official Title: An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab With or Without Chemotherapy, Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: SGN22E-003
  • SECONDARY ID: 2019-004542-15
  • SECONDARY ID: MK-3475-A39
  • NCT ID: NCT04223856

Conditions

  • Urothelial Cancer

Interventions

DrugSynonymsArms
Enfortumab vedotinASG-22CE, ASG-22ME, PADCEVArm A
PembrolizumabKeytrudaArm A
CisplatinArm B
CarboplatinArm B
GemcitabineArm B

Purpose

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together alone or with platinum chemotherapy to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.

Detailed Description

      This study is being conducted to evaluate the combination of enfortumab vedotin +
      pembrolizumab, with or without platinum-containing chemotherapy, versus standard of care
      gemcitabine + platinum-containing chemotherapy, in subjects with previously untreated locally
      advanced or metastatic urothelial cancer.

      Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol
      defined reason for study discontinuation occurs. Pembrolizumab may be administered for a
      maximum of 35 cycles or a protocol-defined reason for study discontinuation occurs, whichever
      is first. Cisplatin, carboplatin, and/or gemcitabine may be administered for a maximum of 6
      cycles or a protocol-defined reason for study discontinuation occurs, whichever is first.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalEnfortumab vedotin + pembrolizumab
  • Enfortumab vedotin
  • Pembrolizumab
Arm BActive ComparatorGemcitabine + cisplatin or carboplatin
  • Cisplatin
  • Carboplatin
  • Gemcitabine
Arm CExperimentalEnfortumab vedotin + pembrolizumab + Cisplatin or carboplatin
  • Enfortumab vedotin
  • Pembrolizumab
  • Cisplatin
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented, unresectable locally advanced or metastatic urothelial
             carcinoma

          -  Measurable disease by investigator assessment according to RECIST v1.1

               -  Participants with prior definitive radiation therapy must have measurable disease
                  per RECIST v1.1 that is outside the radiation field or has demonstrated
                  unequivocal progression since completion of radiation therapy

          -  Participants must not have received prior systemic therapy for locally advanced or
             metastatic urothelial carcinoma with the following exceptions:

               -  Participants that received neoadjuvant chemotherapy with recurrence >12 months
                  from completion of therapy are permitted

               -  Participants that received adjuvant chemotherapy following cystectomy with
                  recurrence >12 months from completion of therapy are permitted

          -  Must be considered eligible to receive cisplatin- or carboplatin-containing
             chemotherapy, in the investigator's judgement

          -  Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of
             metastatic urothelial carcinoma must be provided for PD-L1 testing prior to
             randomization

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2

          -  Adequate hematologic and organ function

        Exclusion Criteria

          -  Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based
             antibody-drug conjugate (ADCs)

          -  Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor
             for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1
             inhibitor or PD-L1 inhibitor

          -  Received prior treatment with an agent directed to another stimulatory or co
             inhibitory T-cell receptor

          -  Received anti-cancer treatment with chemotherapy, biologics, or investigational agents
             not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks
             prior to first dose of study treatment

          -  Uncontrolled diabetes

          -  Estimated life expectancy of less than 12 weeks

          -  Active central nervous system (CNS) metastases

          -  Ongoing clinically significant toxicity associated with prior treatment that has not
             resolved to ≤ Grade 1 or returned to baseline

          -  Currently receiving systemic antimicrobial treatment for active infection (viral,
             bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis
             is permitted.

          -  Known history of hepatitis B, active hepatitis C, or human immunodeficiency virus
             (HIV) infection.

          -  History of another invasive malignancy within 3 years before the first dose of study
             drug, or any evidence of residual disease from a previously diagnosed malignancy

          -  Documented history of a cerebral vascular event (stroke or transient ischemic attack),
             unstable angina, myocardial infarction, or cardiac symptoms consistent with New York
             Heart Association (NYHA) Class IV within 6 months prior to randomization

          -  Receipt of radiotherapy within 2 weeks prior to randomization

          -  Received major surgery (defined as requiring general anesthesia and >24 hour inpatient
             hospitalization) within 3 weeks prior to randomization

          -  Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient
             contained in the drug formulation of enfortumab vedotin

          -  Active keratitis or corneal ulcerations

          -  History of autoimmune disease that has required systemic treatment in the past 2 years

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest computed tomography (CT) scan

          -  Prior allogeneic stem cell or solid organ transplant

          -  Received a live attenuated vaccine within 30 days prior to randomization
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Duration of progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the time from randomization to first documentation of disease progression per RECIST v1.1 by BICR, or to death due to any cause, whichever comes first.

Secondary Outcome Measures

Measure:Duration of PFS per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause, whichever comes first
Measure:Overall response rate (ORR) per RECIST v1.1 by BICR
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1
Measure:ORR per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1
Measure:Duration of response (DOR) per RECIST v1.1 by BICR
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first
Measure:DOR per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first
Measure:Disease control rate (DCR) per RECIST v1.1 by BICR
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1
Measure:DCR per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1
Measure:Change from baseline in patient reported outcome assessment measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire
Time Frame:Up to approximately 5 years
Safety Issue:
Description:The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale.
Measure:Change from baseline in patient reported outcome assessment measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:EORTC-QLQ-C30 is a cancer-specific 30-item questionnaire. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
Measure:Change from baseline in patient reported outcome assessment measured by Brief Pain Inventory - Short Form (BPI-SF)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:The Short Form is a single assessment of overall pain where 0 equals no pain and 10 equals extreme pain. Low pain scores are considered a better outcome than a high pain score.
Measure:Incidence of adverse events (AEs)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Descriptive statistics will be used to summarize results
Measure:Incidence of laboratory abnormalities
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Descriptive statistics will be used to summarize results
Measure:Treatment discontinuation rate due to AEs
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Descriptive statistics will be used to summarize results

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • Urothelial Cancer
  • Enfortumab vedotin
  • metastatic urothelial cancer
  • pembrolizumab
  • locally advanced urothelial cancer

Last Updated

April 21, 2020