Disitamab Vedotin + Pembrolizumab for Bladder Cancer

Recruiting at 272 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: MMAE-based ADCs, HER2-directed

Disqualifiers: Immunodeficiency, Chronic steroids, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 2 years

372 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether the drug disitamab vedotin (an antibody-drug conjugate), either alone or with pembrolizumab (an immunotherapy drug), can effectively treat HER2-expressing urothelial cancer, a type of bladder cancer. Researchers seek to evaluate the effectiveness of these treatments and monitor any side effects. The trial targets individuals with urothelial cancer that has spread locally and cannot be removed or has metastasized. Participants should have this type of cancer and a HER2-positive status, indicating the presence of certain proteins in their cancer cells. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that prior antitumor treatments should not have been received within 2 weeks before starting the study, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the study center.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that disitamab vedotin is generally safe for patients with HER2-positive advanced or metastatic urothelial cancer, a type of bladder cancer. While side effects exist, most patients find them acceptable or manageable.

In studies where disitamab vedotin was used alone, patients tolerated the treatment well. When combined with pembrolizumab, another cancer drug, the combination was also deemed safe for most patients. This indicates that most people can manage the side effects without major issues.

Overall, while side effects can occur, previous research considers the treatment safe. Participants should consult their doctors about possible side effects to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Disitamab Vedotin and Pembrolizumab for bladder cancer because they offer a fresh approach compared to existing treatments like chemotherapy and traditional immunotherapies. Disitamab Vedotin is an antibody-drug conjugate, which means it combines an antibody targeting HER2-positive cancer cells with a potent anti-cancer drug, delivering treatment directly to the tumor and minimizing damage to healthy cells. Pembrolizumab, on the other hand, is a checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, these drugs have the potential to enhance the precision and effectiveness of bladder cancer treatment, offering hope for better outcomes.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that disitamab vedotin holds promise for treating HER2-positive bladder cancer. In one study, 35% of patients experienced a complete response, meaning their cancer disappeared. Another study reported a 75% overall response rate, with 40% of patients experiencing significant tumor shrinkage. In this trial, some participants will receive disitamab vedotin monotherapy, while others will receive a combination of disitamab vedotin and pembrolizumab. Disitamab vedotin, when combined with pembrolizumab—a drug that aids the immune system in fighting cancer—also shows potential. Early data suggest this combination could improve patient outcomes. Overall, these findings provide hope that disitamab vedotin, alone or with pembrolizumab, could effectively treat advanced bladder cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Cohort C: Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra; No prior systemic therapy for LA/mUC; Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy; At least one measurable lesion by investigator assessment based on RECIST v1.1; Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation; HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample; ECOG performance status of 0, 1, or 2

Cohort E: Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra; No prior systemic therapy for LA/mUC; Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy; At least one measurable lesion by investigator assessment based on RECIST v1.1; Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation; HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample; ECOG performance status of 0 or 1

At least one measurable lesion by investigator assessment based on RECIST v1.1.

Exclusion Criteria

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

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

I have not had treatments targeting specific immune system receptors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive disitamab vedotin alone or in combination with pembrolizumab to treat HER2 expressing urothelial cancer

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

Long-term follow-up

Participants are monitored for long-term outcomes such as overall survival and adverse events

Approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Disitamab Vedotin
• Pembrolizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort G - DV monotherapy Experimental Treatment 1 Intervention

Disitamab vedotin

Group II: Cohort E - DV combination therapy (Japan only) Experimental Treatment 2 Interventions

Disitamab vedotin + pembrolizumab

Group III: Cohort D - DV monotherapy (Japan only) Experimental Treatment 1 Intervention

Disitamab vedotin monotherapy

Group IV: Cohort C - Randomized monotherapy Experimental Treatment 1 Intervention

Disitamab vedotin monotherapy

Group V: Cohort C - Randomized combination therapy Experimental Treatment 2 Interventions

Disitamab vedotin + pembrolizumab

Group VI: Cohort C - Non-randomized combination therapy Experimental Treatment 2 Interventions

Disitamab vedotin + pembrolizumab

Group VII: Cohort B - DV monotherapy for HER2-low tumor types Experimental Treatment 1 Intervention

Disitamab vedotin monotherapy

Group VIII: Cohort A - DV monotherapy for HER2-positive tumor types Experimental Treatment 1 Intervention

Disitamab vedotin monotherapy

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

RemeGen Co., Ltd.

Industry Sponsor

Trials

84

Recruited

11,100+

Dr. Jianmin Fang

RemeGen Co., Ltd.

Chief Executive Officer since 2008

PhD in Molecular Biology

Dr. Ruyi He

RemeGen Co., Ltd.

Chief Medical Officer since 2023

MD

Published Research Related to This Trial

In a study of 45 patients with locally advanced or metastatic urothelial cancer, the combination of enfortumab vedotin and pembrolizumab resulted in tumor shrinkage in 73% of patients within 2 months, with effects lasting over 2 years.

While 16% of patients experienced serious side effects, most were manageable, although 24% had to stop treatment due to these side effects, indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. Hoimes, CJ., Flaig, TW., Milowsky, MI., et al.[2023]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

In the PURE-01 study involving 50 patients with muscle-invasive bladder carcinoma, neoadjuvant treatment with pembrolizumab resulted in a pathologic complete response (pT0) in 42% of patients, demonstrating its efficacy as a pre-surgery immunotherapy.

The study found that patients with high PD-L1 expression (CPS ≥ 10%) had a significantly higher rate of pT0 (54.3%) compared to those with lower expression (13.3%), suggesting that pembrolizumab may be particularly effective in patients with PD-L1-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. Necchi, A., Anichini, A., Raggi, D., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, showed a strong antitumor effect in a 70-year-old female patient with unresectable bladder cancer, but it also led to a grade 3 asthma attack as an immune-related adverse event.

The patient's asthma was linked to changes in immune cell markers, specifically increased CTLA-4 and TIM-3 in CD4+ T cells and a rise in Th17 cells, suggesting that these immune responses could be indicators of both adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of bronchial asthma as an immune-related adverse event of pembrolizumab treatment for bladder cancer: A case report. Hamada, K., Yoshimura, K., Oshinomi, K., et al.[2022]

The combination of enfortumab vedotin (EV) and pembrolizumab (Pembro) demonstrated a high confirmed objective response rate (cORR) of 64.5% in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, indicating its efficacy as a first-line treatment option.

Patients receiving the combination therapy also experienced durable responses, with 65.4% maintaining their response at 12 months, while the safety profile showed manageable adverse events, with no new safety signals identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. O'Donnell, PH., Milowsky, MI., Petrylak, DP., et al.[2023]

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

In a study of 36 patients with locally advanced or metastatic urothelial carcinoma, RC48-ADC (disitamab vedotin) demonstrated promising efficacy, with a median progression-free survival (PFS) of 5.4 months and a 1-year overall survival (OS) rate of 79.6%.

Combining RC48 with immunotherapy significantly improved median PFS to 8.5 months compared to 5.4 months for RC48 alone, indicating that this combination may enhance treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study. Chen, M., Yao, K., Cao, M., et al.[2023]

In a study of 528 urothelial carcinoma patients, 44.5% were found to be PD-L1 positive, with higher positivity rates in metastatic sites compared to primary tumors, indicating that the location of the tumor may influence PD-L1 expression.

Genomic profiling revealed that PD-L1 positive patients had more frequent alterations in TP53 and RB1, while PD-L1 negative patients had more FGFR3 alterations, suggesting distinct genomic characteristics that could help predict responses to immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas. Huang, RSP., Haberberger, J., Harries, L., et al.[2021]

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

Disitamab vedotin (DV) showed a promising objective response rate of 50.5% in patients with HER2-positive locally advanced or metastatic urothelial carcinoma who had previously failed standard therapies, based on data from 107 patients in two phase II studies.

The treatment had a manageable safety profile, with the most common adverse events being peripheral sensory neuropathy and leukopenia, though over half of the patients experienced grade ≥3 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials. Sheng, X., Wang, L., He, Z., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02912

Efficacy and Safety of Disitamab Vedotin in Patients With ... DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who had progressed on at ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12355133/

Disitamab vedotin combined with toripalimab and ... The median follow-up time was 12.3 months (range, 10.7-12.8 months). Five patients (83.3 %) achieved a complete response and remained free of ...

3. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-bladder-cancer/154846-esmo-2024-preliminary-efficacy-and-safety-of-disitamab-vedotin-dv-with-pembrolizumab-p-in-treatment-tx-naive-her2-expressing-locally-advanced-or-metastatic-urothelial-carcinoma-la-muc-rc48g001-cohort-c.html

ESMO 2024: Preliminary Efficacy And Safety Of Disitamab ... The confirmed overall response rate (ORR) was 75% (95% CI 50.9-91.3), with 7 patients (35%) achieving a complete response and 8 patients (40%) achieving a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04879329

NCT04879329 | A Study of Disitamab Vedotin Alone or ... This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer.

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14870-x

Clinicopathological and molecular correlates of clinical benefit ... Disitamab Vedotin (DV), a HER-2-targeting antibody-drug conjugate, has exhibited substantial clinical advantages in individuals with metastatic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37988648/

Efficacy and Safety of Disitamab Vedotin in Patients With ... DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666634025000649

Efficacy and safety of DV in HER2-negative and HER2-low ... Disitamab vedotin (DV), an anti-HER2 antibody-drug conjugate (ADC), demonstrates a promising efficacy in patients with HER2-positive mUC.