Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Ureteral Neoplasms

Pelvic Neoplasms

Urologic Neoplasms

Urethral Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ureteral Diseases

Urethral Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Carboplatin

Antibodies

Cisplatin

Immunoglobulins

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Dose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days

Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days

Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days

Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days

Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days

Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days

Enfortumab vedotin on days 1 and 8 every 21 days

Enfortumab vedotin on days 1 and 8 and every 21 days

Intravenous (IV) infusion on days 1 and 8 every 21 days

enfortumab vedotin (EV)

pembrolizumab

cisplatin

carboplatin

IV infusion on days 1 and 8 every 21 days

gemcitabine

Changting Meng, MD

Jason Lukas, MD, PhD

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.

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

multi-cohort, open-label, multicenter study, global

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

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

Descriptive statistics will be used to summarize results.

The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1

The proportion of patients with absence of viable tumor tissue at the time of radical cystectomy.

Incidence of DLTs (dose-escalation expansion Cohorts D, E, F, and the first 6 patients of Cohort G).

The proportion of patients with confirmed CR or PR according to RECIST 1.1.

The proportion of patients with confirmed CR or PR according to RECIST 1.1

The proportion of patients with confirmed CR or PR according to iRECIST.

Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1.

Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1

Proportion of patients with CR, PR, or SD according to iRECIST.

The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD per RECIST 1.1) or to death due to any cause, whichever comes first.

The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per RECIST 1.1 or to death due to any cause, whichever comes first

The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per iRECIST or to death due to any cause, whichever comes first.

The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first.

The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first

The time from start of study treatment to first documentation of objective tumor progression (PD per iRECIST) on or following study therapy, or to death due to any cause, whichever comes first.

The time from the start of study treatment to the first occurrence of any of the following events: (1) Radiographic disease progression precluding a curative intent surgery as assessed by BICR prior to RC+PLND. (2) Failure to undergo RC+PLND for participants with residual muscle-invasive disease and/or any radiographic disease present. (3) Gross residual disease left behind at time of RC+PLND. (4) Local or distant recurrence post-RC as assessed by CT or MRI and/or biopsy. (5) Death from any cause.

The time from start of study treatment to date of death due to any cause.

Cmax will be derived from the PK blood samples collected.

Blood samples for ATA analysis will be collected.

Tmax will be derived from the PK blood samples collected.

AUC will be derived from the PK blood samples collected.

The pDS rate is defined as patients with tumors \<pT2 and N0 in examined tissue from radical cystectomy (RC) and pelvic lymph node dissection (PLND).

DFS is defined as the time from RC to the time of first occurrence of a DFS event, including local recurrence of urothelial cancer (UC), urinary tract recurrence of UC, distant metastasis of UC, or death from any cause.

DFS is defined as the time from RC to the time of first occurrence of a DFS event

Delayed is defined as greater than 12 weeks after the last dose of treatment.

Spots Global Cancer Trial Database for renal pelvis neoplasms