Disitamab Vedotin + Pembrolizumab vs Chemotherapy for Bladder Cancer

Recruiting at 471 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: MMAE agents, Anti-HER2 therapy

Disqualifiers: CNS metastasis, Autoimmune disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 2 years

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining disitamab vedotin (an experimental treatment) and pembrolizumab is more effective than standard chemotherapy for treating urothelial cancer, which affects areas like the bladder and kidneys. Researchers seek to understand how well these drugs work together and identify any side effects. The trial seeks participants whose cancer has spread or is advanced but remains in the same area. It suits those who haven't received major treatments for this type of advanced cancer before. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that disitamab vedotin, used alone or with pembrolizumab, is generally well-tolerated by patients. It has a manageable safety profile for those with advanced bladder cancer. Most reported side effects were mild to moderate, such as tiredness, nausea, and hair loss. Serious side effects were less common but can occur.

The FDA has already approved pembrolizumab for several types of cancer, indicating its well-known safety. When combined with disitamab vedotin, the side effects appear similar. Overall, while some side effects are possible, past studies have found the combination manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about disitamab vedotin combined with pembrolizumab for bladder cancer because this combination brings a novel approach to treatment. Unlike standard chemotherapy options like gemcitabine with cisplatin or carboplatin, disitamab vedotin is an antibody-drug conjugate, which means it delivers chemotherapy directly to cancer cells, potentially reducing damage to healthy cells. Pembrolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells more effectively. Together, these treatments could offer a more targeted and potentially more effective option than traditional chemotherapy alone.

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

In this trial, participants will receive either the combination of disitamab vedotin and pembrolizumab or standard chemotherapy. Studies have shown that this combination looks promising for treating bladder cancer. In earlier research, about 60% to 80% of patients responded well to this treatment. This combination targets cancer cells with a specific marker called HER2 and blocks a protein called PD-1, which helps cancer hide from the immune system. This two-part approach has led to better survival rates compared to chemotherapy alone. These findings strongly support the potential effectiveness of this treatment for patients with advanced bladder cancer. ^{2 3 4 5 6}

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, which includes bladder and kidney cancers. Participants must have measurable disease, be able to receive platinum-based chemo, express a certain level of HER2 protein, and not have had prior systemic therapy for their advanced cancer (with some exceptions). They should also be in a condition that allows daily activities with only slight limitations.

Inclusion Criteria

I haven't had systemic therapy for my bladder cancer, except if it came back 12+ months after initial treatment.

I can be treated with cisplatin or carboplatin chemotherapy.

I can provide a tissue sample from my cancer for testing.

Exclusion Criteria

I have fluid buildup causing symptoms or needing treatment.

My cancer has spread to my brain or its coverings but has been treated.

I have an autoimmune disease that needed treatment in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive disitamab vedotin every two weeks and pembrolizumab every six weeks, or gemcitabine weekly for 2 weeks with cisplatin or carboplatin every 3 weeks

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Through 30 days after the last study treatment

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Disitamab Vedotin
• Gemcitabine
• Pembrolizumab

Trial Overview The study compares the effectiveness of disitamab vedotin combined with pembrolizumab versus standard chemotherapy (gemcitabine with cisplatin or carboplatin) in treating urothelial cancer. Patients are randomly placed into two groups: one receiving the new drug combination and the other receiving traditional chemotherapy.

How Is the Trial Designed?

Group I: Disitamab vedotin arm Experimental Treatment 2 Interventions

disitamab vedotin + pembrolizumab

Group II: Standard of care arm Active Control 3 Interventions

gemcitabine + cisplatin OR carboplatin

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

Pembrolizumab, a checkpoint inhibitor, has been shown to significantly improve overall survival in patients with locally advanced or metastatic urothelial carcinoma who have progressed after cisplatin-containing chemotherapy, compared to standard chemotherapy options.

Additionally, evidence from Phase 1 and 2 trials suggests that checkpoint inhibitors like pembrolizumab are effective as a first-line treatment for patients who cannot tolerate cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of bladder cancer. Sundahl, N., Rottey, S., De Maeseneer, D., et al.[2018]

In a study of 45 cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, the combination of enfortumab vedotin and pembrolizumab resulted in a high confirmed objective response rate of 73.3%, indicating significant tumor shrinkage.

The treatment demonstrated a manageable safety profile, with most adverse events being manageable, and showed promising median durations of response and overall survival of 25.6 months and 26.1 months, respectively, suggesting its potential as an effective first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. Hoimes, CJ., Flaig, TW., Milowsky, MI., et al.[2023]

In a study of 140 patients with non-metastatic muscle-invasive bladder cancer, both gemcitabine plus cisplatin (Gem/Cis) and gemcitabine plus carboplatin (Gem/Carbo) regimens showed similar rates of complete clinical response (cCR) before surgery, indicating that both treatments are effective in this context.

However, patients receiving Gem/Cis had significantly better overall survival (OS) compared to those on Gem/Carbo, with median OS of 41 months versus 26 months, suggesting that while both regimens are effective, Gem/Cis may offer a survival advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis. Mofid, B., Razzaghdoust, A., Ghajari, M., et al.[2022]

Five checkpoint inhibitors, including pembrolizumab and atezolizumab, are FDA-approved for treating advanced metastatic urothelial carcinoma after progression on cisplatin-based chemotherapy, showing significant clinical efficacy.

For patients who are eligible for cisplatin, standard first-line treatment remains platinum-based chemotherapy, but for those who progress, pembrolizumab has shown superior results compared to standard chemotherapy in phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approved checkpoint inhibitors in bladder cancer: which drug should be used when? Ghatalia, P., Zibelman, M., Geynisman, DM., et al.[2020]

In a study of 17 elderly patients (median age 78) with nonoperable transitional cell carcinoma of the bladder, carboplatin demonstrated sufficient activity, achieving a 53% complete response rate, particularly in patients with T2 tumors.

The treatment was well-tolerated, with only 41% of patients experiencing moderate hematologic toxicity, and over 30% remained free from disease progression at 24 months, suggesting carboplatin is a promising option for further phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin monochemotherapy in elderly patients with nonoperable transitional cell carcinoma of the bladder: a two-stage, phase II study. Segati, R., Bari, M., Azzarello, G., et al.[2019]

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]

A 68-year-old man with muscle-invasive bladder cancer and severe renal insufficiency successfully received neoadjuvant therapy with gemcitabine and Disitamab Vedotin, resulting in significant reduction of tumor lesions as shown by imaging.

The treatment was well-tolerated, with no significant adverse side effects reported, indicating that this combination therapy may be a safe alternative for patients who cannot tolerate platinum-based regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy with Disitamab vedotin in treating muscle-invasive bladder cancer: A case report. Huang, H., Zhang, Y., Chen, Z., et al.[2023]

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]

Cisplatin is a key treatment for bladder cancer, but managing its side effects, like nausea and acute kidney injury, is crucial to maintain treatment effectiveness and avoid dose reductions.

An effective strategy for preventing cisplatin-associated nausea and vomiting involves a four-drug prophylactic regimen, while intensive hydration is essential for preventing acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of cisplatin-associated toxicities in bladder cancer patients. Desilets, A., Adam, JP., Soulières, D.[2021]

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

Citations

1. 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 ... Novel biomarkers may help inform treatment strategies and potentially improve outcomes further. Data confirm that approximately 60% to 80% of patients with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4616

Phase 3 study of disitamab vedotin with pembrolizumab vs ... Improved outcomes observed with an MMAE payload plus PD-1 inhibition across the ADC landscape, along with DV data, provide a robust rationale ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12407659/

SGNDV-001: disitamab vedotin with pembrolizumab in HER2 ... In the EV-302 trial, the combination of enfortumab vedotin with pembrolizumab improved survival outcomes versus chemotherapy in the first-line setting [5].

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. nejm.org nejm.org/doi/full/10.1056/NEJMoa2511648?query=featured_home

Disitamab Vedotin plus Toripalimab in HER2-Expressing ... Previous data showed promising antitumor activity and safety of HER2-specific disitamab vedotin as monotherapy and when combined with programmed ...

6. 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.