What side effects are associated with this type of intervention?

Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, has been associated with side effects such as fatigue, peripheral neuropathy, rash, and hyperglycemia. Immune checkpoint inhibitors like pembrolizumab, used in the treatment of bladder cancer, commonly cause side effects including fatigue, rash, pruritus, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. These treatments aim to manage advanced urothelial carcinoma but come with a range of potential side effects that should be monitored closely.

What prior FDA approvals exist?

Enfortumab Vedotin is an antibody-drug conjugate targeting Nectin-4, and it has been approved by the FDA for the treatment of advanced urothelial carcinoma, particularly in patients who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. Other FDA-approved treatments for bladder cancer include immune checkpoint inhibitors such as Pembrolizumab and Atezolizumab, which target PD-1 and PD-L1, respectively. These treatments have shown efficacy in patients with advanced or metastatic urothelial carcinoma, providing additional options for those who have progressed on or are ineligible for traditional chemotherapy.

What other types of research exist?

Promising alternatives to Enfortumab Vedotin for bladder cancer patients include immune checkpoint inhibitors such as pembrolizumab and nivolumab. Combination therapies involving these agents, like nivolumab plus ipilimumab, are also potential options. Experimental therapies, including chimeric antigen receptor (CAR)-T cell therapies, are being tested and may offer new avenues for treatment.

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Antibody-Drug Conjugate

Enfortumab Vedotin for Bladder Cancer (EV-103 Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Astellas Pharma Global Development, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

MIBC - Cohorts H, J, and L: Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC

MIBC - Cohorts H, J, and L: Received any prior treatment with a CPI

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called enfortumab vedotin alone and with other treatments in patients with advanced or muscle-invasive bladder cancer. The goal is to see how well these treatments work and what side effects they might have. Enfortumab vedotin targets and kills cancer cells, while pembrolizumab helps the immune system fight the cancer.

Who is the study for?

This trial is for adults with advanced or muscle-invasive urothelial cancer, including bladder and other urinary cancers. Participants should be eligible for certain chemotherapy drugs like cisplatin or carboplatin, and some may also qualify for pembrolizumab treatment. They must not have received specific prior treatments, have a good performance status (able to carry out daily activities), and an expected lifespan of at least 3 months.

What is being tested?

The study tests enfortumab vedotin alone or combined with anticancer therapies such as pembrolizumab, cisplatin, carboplatin, and gemcitabine. It aims to see if these treatments can shrink the cancer in patients with locally advanced or metastatic urothelial cancer as well as those with muscle-invasive bladder cancer.

What are the potential side effects?

Possible side effects include reactions related to the immune system affecting organs, infusion-related reactions from the drug entering the body, fatigue, digestive issues like nausea or diarrhea, blood disorders that affect cell counts and increase infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can't have cisplatin and haven't been treated for advanced bladder cancer, or my cancer got worse after platinum treatment.

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My cancer got worse or came back after treatment with a platinum-based drug.

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I can take care of myself and am up and about more than half of my waking hours.

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My bladder cancer diagnosis was confirmed through tissue examination.

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I cannot receive cisplatin as a treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had surgery to remove part of my bladder for cancer.

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I have had prior treatment with a checkpoint inhibitor.

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I have ongoing nerve issues in my senses or movements that are moderate to severe.

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I am not on high doses of steroids or other drugs that weaken my immune system.

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I have been treated with enfortumab vedotin or similar drugs before.

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I am experiencing significant side effects from previous cancer treatments.

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I am on high doses of steroids or other drugs that weaken my immune system.

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I have had treatment with enfortumab vedotin or similar drugs for bladder cancer.

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I had another type of cancer within the last 3 years.

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I have had treatment for muscle invasive bladder cancer before.

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My cancer has spread to my brain or spinal cord.

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My diabetes is not under control.

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I have ongoing nerve issues in my senses or movements that are moderate to severe.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) (Cohort K only)

Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only)

Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3 cohorts only)

+1 more

Secondary study objectives

Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Cohort A only)

Confirmed ORR by investigator assessment according to RECIST 1.1 (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)

+29 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: Randomized Cohort K: Enfortumab Vedotin MonotherapyExperimental Treatment1 Intervention

Enfortumab vedotin on days 1 and 8 every 21 days

Group II: Randomized Cohort K: Enfortumab Vedotin + PembrolizumabExperimental Treatment2 Interventions

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

Group III: Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant settingExperimental Treatment2 Interventions

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

Group IV: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2LExperimental Treatment2 Interventions

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

Group V: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2LExperimental Treatment2 Interventions

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

Group VI: EV + Pembrolizumab in cisplatin-ineligible 1L and in 2LExperimental Treatment2 Interventions

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

Group VII: Cohort L: Enfortumab vedotin in MIBC in perioperative settingExperimental Treatment1 Intervention

Enfortumab vedotin on days 1 and 8 and every 21 days

Group VIII: Cohort H: Enfortumab vedotin in MIBC neoadjuvant settingExperimental Treatment1 Intervention

Enfortumab vedotin on days 1 and 8 every 21 days

Group IX: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1LExperimental Treatment4 Interventions

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

Group X: Cohort E: Enfortumab Vedotin + Carboplatin in 1LExperimental Treatment2 Interventions

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

Group XI: Cohort D: Enfortumab Vedotin + Cisplatin in 1LExperimental Treatment2 Interventions

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

Group XII: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1LExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

carboplatin

2010

Completed Phase 3

~4790

gemcitabine

2013

Completed Phase 3

~4260

pembrolizumab

2017

Completed Phase 3

~5890

cisplatin

1997

Completed Phase 3

~3290

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Bladder cancer treatments often include chemotherapy, immunotherapy, and targeted therapies. Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, works by delivering a cytotoxic agent directly to cancer cells expressing Nectin-4, thereby minimizing damage to healthy cells. Immunotherapies like pembrolizumab and atezolizumab inhibit PD-1/PD-L1 pathways, enhancing the immune system's ability to attack cancer cells. These treatments are crucial for bladder cancer patients as they offer targeted approaches that can improve efficacy and reduce side effects compared to traditional chemotherapy, potentially leading to better outcomes and quality of life.

[The role of immunotherapy in the modern treatment of urothelial carcinoma].