Disitamab Vedotin + Pembrolizumab vs Chemotherapy for Bladder Cancer

Recruiting at 359 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

Trial Summary

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.

What data supports the effectiveness of the drugs Disitamab Vedotin and Pembrolizumab for bladder cancer?

Pembrolizumab has shown effectiveness as a second-line treatment for advanced bladder cancer, especially in patients who cannot tolerate cisplatin. Disitamab Vedotin has been used in a case where traditional platinum-based treatments were not suitable, indicating potential effectiveness in certain patients. ^{1 2 3 4 5}

Is the combination of Disitamab Vedotin and Pembrolizumab safe for bladder cancer treatment?

Carboplatin, a component of the treatment, has been shown to have acceptable toxicity levels in elderly bladder cancer patients, with manageable side effects. Pembrolizumab, another component, is a well-tolerated treatment option for patients who cannot use cisplatin-based therapies, offering a new alternative with a different safety profile. ^{1 6 7 8 9}

How is the drug combination of Disitamab Vedotin and Pembrolizumab different from other bladder cancer treatments?

The combination of Disitamab Vedotin and Pembrolizumab offers a novel approach for bladder cancer patients who cannot tolerate traditional platinum-based chemotherapy, as it combines a targeted therapy with an immune checkpoint inhibitor, potentially providing a more effective and tolerable option for those ineligible for cisplatin. ^{2 3 8 9 10}

What is the purpose of this trial?

This study will enroll participants with urothelial cancer (UC). UC can include cancer of the bladder, kidney, or the tubes that carry pee through the body (ureter, urethra). This study will try to find out if the drugs disitamab vedotin with pembrolizumab works better than platinum-containing chemotherapy to treat patients with UC. This study will also test what side effects happen when participants take these drugs together. A side effect is anything a drug does to the body besides treating the disease. Participants in this study will have cancer that has spread through the body (metastatic) or spread near where it started (locally advanced). In this study, there are 2 different groups. Participants will be assigned to a group randomly. Participants in the disitamab vedotin arm will get the study drug disitamab vedotin once every two weeks and pembrolizumab once every 6 weeks. Participants in the standard of care arm will get gemcitabine once a week for 2 weeks with either cisplatin or carboplatin once every 3 weeks.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Iran pubmed.ncbi.nlm.nih.gov

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy with Disitamab vedotin in treating muscle-invasive bladder cancer: A case report. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Approved checkpoint inhibitors in bladder cancer: which drug should be used when? [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. [2022]

5. United States 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. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Carboplatin monochemotherapy in elderly patients with nonoperable transitional cell carcinoma of the bladder: a two-stage, phase II study. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Management of cisplatin-associated toxicities in bladder cancer patients. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of bladder cancer. [2018]