Sacituzumab + Enfortumab With/Without Pembrolizumab for Bladder Cancer

Recruiting at 22 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids, Live vaccines, others

Disqualifiers: Active cancer, CNS metastases, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 2

98 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or systemic steroids, you may need to stop them before starting Part 2 of the study.

What data supports the effectiveness of the drug combination Sacituzumab + Enfortumab for bladder cancer?

The drug enfortumab vedotin has been approved by the FDA for treating advanced bladder cancer, showing a 44% response rate in patients who had previously received other treatments. This suggests it could be effective in combination with other drugs for bladder cancer. ^{1 2 3 4 5}

Is the combination of Sacituzumab and Enfortumab safe for treating bladder cancer?

Enfortumab Vedotin, used for advanced bladder cancer, has shown some safety concerns, including high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. In a study, 73% of patients experienced serious side effects. ^{1 2 3 4 6}

What makes the drug combination of Sacituzumab, Enfortumab, and Pembrolizumab unique for bladder cancer?

This drug combination is unique because it combines two antibody-drug conjugates, Sacituzumab and Enfortumab, which target different proteins on cancer cells, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer. This multi-targeted approach is novel for treating advanced bladder cancer, especially in patients who have already received other treatments. ^{1 3 4 5 7}

What is the purpose of this trial?

This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the safety and preliminary efficacy of sacituzumab tirumotecan plus enfortumab vedotin (EV). Part 2 will be based on Part 1 results and will evaluate the efficacy, pharmacokinetics, and safety of sacituzumab tirumotecan plus EV in combination with pembrolizumab in participants with advanced urothelial carcinoma.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced urothelial carcinoma, a type of bladder cancer. Participants should not have had certain previous treatments and must be in good physical condition to handle the study drugs. Specific criteria will determine who can join based on their medical history and current health status.

Inclusion Criteria

My side effects from previous cancer treatments have mostly gone away.

I can provide a sample of my tumor for testing, either from a new biopsy or an existing sample.

I have had no more than 2 treatments for my bladder cancer.

Exclusion Criteria

I have or had inflammatory bowel disease like Crohn's or ulcerative colitis.

I have another cancer that is getting worse or was treated in the last 3 years.

Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive sacituzumab tirumotecan plus enfortumab vedotin (EV) to evaluate safety and preliminary efficacy

Up to 2 years

IV infusions on Days 1 and 8 of every 3-week cycle

Treatment Part 2

Based on Part 1 results, participants receive sacituzumab tirumotecan plus EV in combination with pembrolizumab to evaluate efficacy, pharmacokinetics, and safety

Up to 2 years

IV infusions on Days 1 and 8 of every 3-week cycle, pembrolizumab on Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Enfortumab Vedotin
• Pembrolizumab
• Sacituzumab Tirumotecan

Trial Overview The study tests Sacituzumab Tirumotecan plus Enfortumab Vedotin (EV), with or without Pembrolizumab, for treating advanced bladder cancer. It's divided into two parts: first assessing safety and early results, then evaluating effectiveness and side effects when combined with Pembrolizumab.

Participant Groups

Group I: Sacituzumab tirumotecan plus EV and pembrolizumab Experimental Treatment 3 Interventions

Participants will receive sacituzumab tirumotecan as an IV infusion and EV as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision. Participants will also receive pembrolizumab 200 mg as an IV infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles).

Group II: Sacituzumab tirumotecan plus EV Experimental Treatment 2 Interventions

Participants will receive sacituzumab tirumotecan as an intravenous (IV) infusion and EV as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Padcev for:

• Locally advanced or metastatic urothelial cancer

Approved in European Union as Padcev for:

• Locally advanced or metastatic urothelial cancer

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

Findings from Research

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

Enfortumab vedotin-ejfv (EV) is an effective treatment for locally advanced or metastatic urothelial carcinoma (UC), showing a 44% overall response rate and a median overall survival of 11.7 months in heavily pretreated patients.

While EV demonstrates significant antitumor activity, it also presents unique toxicity concerns that require careful monitoring, highlighting the need for further studies to optimize its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. Halford, Z., Anderson, MK., Clark, MD.[2021]

In a phase I trial involving 23 patients with metastatic urothelial carcinoma, the combination of sacituzumab govitecan (SG) and enfortumab vedotin (EV) demonstrated a high objective response rate of 70%, with three patients achieving complete responses.

The study identified a safe dose for further testing, with 78% of patients experiencing grade ≥3 adverse events, indicating that while the treatment is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. McGregor, BA., Sonpavde, GP., Kwak, L., et al.[2023]

Enfortumab vedotin (PADCEV) received accelerated FDA approval for treating locally advanced or metastatic urothelial cancer in patients who have already undergone specific prior therapies, based on substantial evidence from a study involving 125 patients.

The treatment showed a confirmed objective response rate of 44%, with a median response duration of 7.6 months, although 73% of patients experienced grade 3-4 adverse reactions, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. Chang, E., Weinstock, C., Zhang, L., et al.[2022]

Enfortumab vedotin and sacituzumab govitecan are novel antibody-drug conjugates that improve treatment options for patients with advanced bladder cancer after they have received platinum-based therapy and immune checkpoint inhibitors, with enfortumab vedotin showing improved overall survival.

Sacituzumab govitecan has a 27% response rate in treating advanced bladder cancer, highlighting its potential effectiveness, but careful consideration of the safety profiles of both agents is essential for optimizing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of enfortumab vedotin and sacituzumab govitecan in treatment of advanced bladder cancer. Hanna, KS., Larson, S., Nguyen, J., et al.[2022]

Enfortumab vedotin is an FDA-approved treatment for advanced or metastatic urothelial carcinoma (UC) that has shown a significant objective response rate of 44% in the EV-201 trial.

Patients receiving enfortumab vedotin need to be monitored for potential side effects, including peripheral neuropathy, rash, and hyperglycemia, highlighting the importance of safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancements in Therapy for Bladder Cancer: Enfortumab Vedotin. Hanna, KS.[2021]

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]

References

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

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. [2023]

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

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]

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

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. [2023]

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

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The role of enfortumab vedotin and sacituzumab govitecan in treatment of advanced bladder cancer. [2022]

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

Advancements in Therapy for Bladder Cancer: Enfortumab Vedotin. [2021]

7. England 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. [2023]