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

Official Title

A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer

Summary:

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 and metastatic urothelial cancer, 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.

Trial Description

Primary Outcome:

  • Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • Pathological complete response (pCR) rate per central pathology review (MIBC coohorts only)
  • Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) by blinded independent central review (BICR) (Cohort K only)
Secondary Outcome:
  • Incidence of dose-limiting toxicity (DLT)
  • Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
  • Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • Confirmed ORR by investigator assessment per the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
  • Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
  • DCR by BICR according to RECIST 1.1 (la/mUC cohorts only)
  • DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only)
  • Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
  • DOR by BICR according to RECIST 1.1 (la/mUC cohorts only)
  • DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
  • Progression free survival on study therapy (PFS) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
  • Progression free survival on study therapy (PFS) by BICR according to RECIST 1.1 (la/mUC cohorts only)
  • PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
  • Event-free (EFS) on study therapy by BICR (Cohort L only)
  • Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only)
  • Overall survival (OS) (all cohorts)
  • Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized (la/mUC cohorts only)
  • PK parameter for monomethyl auristatin E (MMAE): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • PK parameter for MMAE: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • PK parameter for MMAE: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
  • pCR rate by local pathology review (MIBC cohorts only)
  • Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only)
  • pDS rate by local pathology review (MIBC cohorts only)
  • Disease-free survival (DFS) by investigator assessment (MIBC cohorts only)
  • DFS by BICR (Cohort L only)
  • Type, incidence, severity, seriousness, and relatedness of AEs (Randomized Cohort K and MIBC cohorts only)
  • Type, incidence, and severity of laboratory abnormalities (Randomized Cohort K and MIBC cohorts only)
  • Percentage of planned surgeries delayed due to treatment-related AEs (MIBC cohorts only)
This study will examine the safety and anticancer activity of enfortumab vedotin (EV) given intravenously as monotherapy and in combination with other anticancer therapies as first line (1L) and second line (2L) treatment for patients with urothelial cancer. The primary goal of the study is to determine the safety, tolerability, and efficacy of enfortumab vedotin alone and in combination with pembrolizumab and/or chemotherapy. The study will be conducted in multiple parts: Locally advanced or metastatic urothelial cancer:
  • Dose escalation
  • Expansion
  • Part 1: Cohorts A and Optional B
  • Part 2: Cohorts D, E, and Optional F
  • Part 3: Cohort G.
  • Randomized Cohort K
  • EV Monotherapy Arm
  • EV Combination Arm Muscle invasive bladder cancer:
  • Cohort H
  • Optional Cohort J
  • Cohort L

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society