Trial Search Results

A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer

This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to treat patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of the study will look at locally advanced or metastatic urothelial cancer (la/mUC), which means the cancer has spread to nearby tissues or to other areas of the body. Other parts of the study will look at muscle-invasive bladder cancer (MIBC), which is cancer at an earlier stage that has spread into the muscle wall of the bladder. This study will look at the side effects of enfortumab vedotin alone and with other anticancer therapies. A side effect is a response to a drug that is not part of the treatment effect. This study will also test if the cancer shrinks with the different treatment combinations.

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

Astellas Pharma Global Development, Inc.

Collaborator: Merck Sharp & Dohme LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: enfortumab vedotin (EV)
  • Drug: pembrolizumab
  • Drug: cisplatin
  • Drug: carboplatin
  • Drug: gemcitabine

Phase:

Phase 1/Phase 2

Eligibility


Inclusion Criteria:

   - Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G
   and K.

      - Histologically documented la/mUC, including squamous differentiation or mixed
      cell types.

      - An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or
      2: Participants with ECOG performance status of 2 must meet the following
      additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class
      III heart failure.

      - Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K
      Combination Arm).

      - Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy
      and no prior treatment for la/mUC, or have disease progression following at least
      1 platinum-containing treatment.

      - Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for
      la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12
      months.

      - Cohort B: Must have disease progression during/following treatment with at least
      1 platinum-containing regimen for la/mUC or disease recurrence.

      - Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for
      la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12
      months.

      - Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin,
      and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based
      therapy in at least 12 months.

      - Cohort F: Ineligible for platinum-based chemotherapy, or disease progression
      during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.

      - Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or
      carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant
      platinum-based therapy in at least 12 months.

      - Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the
      following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG
      performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York
      Heart Association (NYHA) Class III heart failure. No prior systemic treatment for
      locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based
      therapy within 12 months prior to randomization.

   - Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.

      - Histologically confirmed MIBC with predominant >50% urothelial histology: Cohorts
      H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or
      cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1
      disease on imaging. Mixed cell types are eligible if urothelial cancer is
      predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors
      are ineligible regardless of component percentage. Urothelial tumors not
      originating in the bladder (eg, upper tract tumors, urethral tumors) are
      ineligible.

      - Must be cisplatin-ineligible.

      - Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment,
      chemoradiation, or radiation therapy for MIBC. May have received prior
      intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for
      non-MIBC; Cohort J: Eligible for pembrolizumab.

      - ECOG performance status of 0, 1, or 2.

      - Anticipated life expectancy of ≥3 months.

      - Tumor samples with an associated pathology report from the diagnostic
      transurethral resection of a bladder tumor done 90 days prior to the first dose
      of study treatment must be available prior to enrollment and determined to be
      sufficient for pathology review and biomarker analysis.

      - Participants must be deemed eligible for RC+PLND.

Exclusion Criteria:

   - la/mUC - Cohorts A, B, D, E, F, G, and K

      - Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2
      inhibitor, except Cohort F.

      - Received any prior treatment with stimulatory or co-inhibitory T-cell receptor
      agents, such as CD137 agonists, OX-40 agonists, or cytotoxic
      T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).

      - Ongoing sensory or motor neuropathy Grade 2 or higher.

      - Active central nervous system (CNS) metastases.

      - Ongoing clinically significant toxicity (Grade 2 or greater) associated with
      prior treatment (including radiotherapy or surgery).

      - Conditions requiring high doses of steroids or other immunosuppressive
      medications.

      - Prior treatment with enfortumab vedotin or other monomethyl auristatin E
      (MMAE)-based antibody-drug conjugates (ADCs).

      - Uncontrolled diabetes mellitus.

   - MIBC - Cohorts H, J, and L

      - Received prior systemic treatment, chemoradiation, and/or radiation therapy of
      muscle invasive bladder cancer.

      - Received any prior treatment with a CPI.

      - Received any prior treatment with stimulatory or co-inhibitory T-cell receptor
      agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.

      - For participants in Cohort H, evidence of nodal disease on imaging. For
      participants in Cohort L, ≥N2 nodal disease on imaging.

      - Participant has undergone partial cystectomy of the bladder to remove any NMIBC
      or MIBC.

      - Ongoing sensory or motor neuropathy Grade 2 or higher.

      - Conditions requiring high doses of steroids or other immunosuppressive
      medications.

      - Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial
      cancer.

      - Participants with a history of another invasive malignancy within 3 years before
      first dose of study drug.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Paige Baker
650-736-3687
Not Recruiting