What side effects are associated with this type of intervention?

Common treatments for bladder cancer, especially those targeting HER2 like Disitamab Vedotin, often have side effects such as fatigue, nausea, and increased liver function tests. Specific to antibody-drug conjugates, side effects can include neutropenia, peripheral neuropathy, and gastrointestinal issues. Chemotherapy regimens may cause neutropenic sepsis, nephrotoxicity, and cardiotoxicity, while immunotherapies like pembrolizumab can lead to immune-related adverse events such as colitis, hepatitis, and endocrinopathies.

What prior FDA approvals exist?

For the treatment of bladder cancer, the FDA has approved several therapies, including antibody-drug conjugates (ADCs) and immune checkpoint inhibitors. Enfortumab Vedotin, an ADC targeting Nectin-4, is one such example approved for patients with advanced urothelial carcinoma who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. While Disitamab Vedotin targets HER2, similar ADCs like Trastuzumab Emtansine have been used in other cancers such as breast cancer. These therapies work by delivering cytotoxic agents directly to cancer cells expressing specific antigens, thereby minimizing systemic toxicity.

What other types of research exist?

Promising novel alternatives to Disitamab Vedotin for bladder cancer patients in 2024 include immune checkpoint inhibitors such as pembrolizumab and nivolumab. These agents can be used alone or in combination with other therapies. Additionally, ongoing research into other targeted therapies and combination regimens may provide new options.

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Antibody-Drug Conjugate

Disitamab Vedotin + Pembrolizumab for Bladder Cancer

Phase 2

Recruiting

Research Sponsored by Seagen Inc.

Eligibility Criteria Checklist

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

Must have

Cohorts A and B: Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra

Cohort D: Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra

Must not have

Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B)

Cohort C: Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components

Timeline

Screening 3 weeks

Treatment Varies

Follow Up duration of study; approximately 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called disitamab vedotin, alone or with pembrolizumab, for patients with advanced or metastatic HER2 expressing bladder cancer. Disitamab vedotin is designed to target HER2 and has been approved for other types of cancer. The study aims to see if these drugs can effectively treat the cancer and what side effects they might cause.

Who is the study for?

This trial is for adults with advanced urothelial cancer that expresses HER2 and can't be removed by surgery or has spread. They should have had certain prior treatments, including platinum chemotherapy and PD-(L)1 inhibitors. Participants need to have at least one measurable tumor lesion, an ECOG performance status of 0-2, and no recent other cancer therapies.

What is being tested?

The study tests disitamab vedotin alone or combined with pembrolizumab in treating HER2 expressing urothelial cancer. It aims to evaluate the effectiveness and safety of these drugs in patients whose cancer is locally advanced or metastatic.

What are the potential side effects?

Possible side effects include reactions related to drug infusion, nerve damage (neuropathy), immune system complications affecting organs, fatigue, hair loss not beyond Grade 2 alopecia, and any previous treatment-related issues must be mild except for hair loss.

Eligibility Criteria

Inclusion Criteria

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

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My cancer originates from the urinary system and cannot be surgically removed.

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My cancer originates from the urinary system.

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My cancer's HER2 status is confirmed to be 1+, 2+, or 3+.

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I am fully active or can carry out light work.

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I am able to care for myself and perform daily activities.

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I have previously been treated with enfortumab vedotin.

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I've had 1 or 2 treatments for my bladder cancer, including a platinum-based chemotherapy.

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I have had one treatment with platinum-based chemotherapy.

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I have previously been treated with PD-(L)1 inhibitors.

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I am fully active or can carry out light work.

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I have completed all standard care treatments for my condition in Japan.

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My cancer originates from the urinary system.

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My cancer's HER2 status is 1+, 2+, or 3+ based on a lab test.

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I have not had any drug treatments for my advanced bladder cancer.

Exclusion Criteria

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

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I haven't had cancer treatment in the last 2 weeks.

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I am not allergic to disitamab vedotin, pembrolizumab, or their ingredients.

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I have not had treatments targeting specific immune system receptors.

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I have mild or worse nerve damage in my hands or feet.

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I have experienced severe side effects from previous treatments.

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I have previously received treatments targeting HER2 or using antibody-drug conjugates.

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My side effects from past treatments are still severe, except for hair loss.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I have moderate to severe numbness, tingling, or muscle weakness.

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I am not allergic to disitamab vedotin, pembrolizumab, or their ingredients.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ duration of study; approximately 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~duration of study; approximately 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and duration of study; approximately 3 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 (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) (Cohorts A, B, and C)

Incidence of adverse events (AEs) (Cohorts D and E)

Incidence of laboratory abnormalities (Cohorts D and E)

+4 more

Secondary study objectives

Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C)

Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, and C)

DCR per RECIST v1.1 by investigator (Cohorts A, B, and C)

+16 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

7Treatment groups

Experimental Treatment

Group I: Cohort E - DV combination therapy (Japan only)Experimental Treatment2 Interventions

Disitamab vedotin + pembrolizumab

Group II: Cohort D - DV monotherapy (Japan only)Experimental Treatment1 Intervention

Disitamab vedotin monotherapy

Group III: Cohort C - Randomized monotherapyExperimental Treatment1 Intervention

Disitamab vedotin monotherapy

Group IV: Cohort C - Randomized combination therapyExperimental Treatment2 Interventions

Disitamab vedotin + pembrolizumab

Group V: Cohort C - Non-randomized combination therapyExperimental Treatment2 Interventions

Disitamab vedotin + pembrolizumab

Group VI: Cohort B - DV monotherapy for HER2-low tumor typesExperimental Treatment1 Intervention

Disitamab vedotin monotherapy

Group VII: Cohort A - DV monotherapy for HER2-positive tumor typesExperimental Treatment1 Intervention

Disitamab vedotin monotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

pembrolizumab

2017

Completed Phase 3

~5890

0 / 24Eligibility 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

The most common treatments for bladder cancer include antibody-drug conjugates (ADCs) like Disitamab Vedotin, which target HER2-expressing cancer cells. ADCs combine the specificity of antibodies with the cytotoxic potency of chemotherapy, delivering the drug directly to the tumor and minimizing damage to normal cells. This targeted approach can reduce side effects and improve treatment efficacy. Additionally, immune checkpoint inhibitors like pembrolizumab enhance the body's immune response against cancer cells by blocking proteins that inhibit immune activity. These mechanisms are crucial for personalizing treatment plans and improving outcomes for bladder cancer patients.

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