Sacituzumab Tirumotecan for Bladder Cancer

(TroFuse-027 Trial)

Recruiting at 4 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: High-grade NMIBC, MIBC, Metastatic UC, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of the study is to learn about the safety of Sacituzumab Tirumotecan and if people can tolerate it when given in the bladder and find the highest dose that people can take without having certain problems. Researchers will then choose a dose level of Sacituzumab Tirumotecan to use in future studies to learn how well the drug works.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Sacituzumab Tirumotecan for bladder cancer?

Sacituzumab govitecan, a similar drug, has shown promising results in treating advanced bladder cancer, particularly for patients who have not responded to other treatments. It targets a protein called Trop-2, which is often found in high amounts in bladder cancer cells, and has been effective in early clinical trials, leading to its accelerated approval for certain patients. ^{1 2 3 4 5}

Is Sacituzumab Tirumotecan safe for humans?

Sacituzumab govitecan, a similar treatment, has been used for breast and urothelial cancer, but it can cause side effects like neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). Most side effects occur within 30 days of starting treatment, and men may have a higher risk of serious side effects leading to hospitalization. ^{1 2 3 6 7}

How is the drug Sacituzumab Tirumotecan unique for bladder cancer treatment?

Sacituzumab Tirumotecan, similar to Sacituzumab Govitecan, is an antibody-drug conjugate that targets Trop-2, a protein often found in high amounts on bladder cancer cells, and delivers a chemotherapy agent directly to these cells. This targeted approach can potentially improve effectiveness and reduce side effects compared to traditional chemotherapy. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for people with recurrent low-grade bladder cancer that hasn't spread into muscle. They should have had a tumor seen by cystoscopy within the last 12 weeks, possibly multiple tumors or frequent recurrences, and may have failed previous treatments. Participants need to be relatively active and well (ECOG status 0-2).

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My tumor is larger than 3 cm and it's the only one.

My previous bladder treatments did not work.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical Sacituzumab Tirumotecan for 6 weeks

6 weeks

Dose Limiting Toxicity Evaluation

Evaluation of dose limiting toxicity during the treatment period

7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Monitoring of complete response and adverse events over an extended period

24 months

Treatment Details

Interventions

• Sacituzumab Tirumotecan (Monoclonal Antibodies)

Trial Overview Researchers are testing Sacituzumab Tirumotecan given directly in the bladder to find a safe and tolerable dose. This chosen dose will then be used in future studies to see how effective it is against bladder cancer.

Participant Groups

Group I: Sacituzumab tirumotecan Experimental Treatment 1 Intervention

Participants receive intravesical Sacituzumab Tirumotecan for 6 weeks

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

Sacituzumab govitecan (SG) is an effective treatment for locally advanced and metastatic urothelial cancer, showing a 27% objective response rate in the TROPHY-U-01 phase II trial.

While SG has common side effects like diarrhea and neutropenia, these can be managed with supportive care, and it has received accelerated approval for patients who have previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitor treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. Mathew Thomas, V., Tripathi, N., Agarwal, N., et al.[2022]

In a phase II study involving 113 patients with metastatic urothelial carcinoma who had previously progressed on platinum-based chemotherapy and checkpoint inhibitors, sacituzumab govitecan (SG) demonstrated an objective response rate of 27%, indicating significant efficacy in this difficult-to-treat population.

SG was associated with a manageable safety profile, with the most common severe side effects being neutropenia (35%) and diarrhea (10%), leading to a 6% discontinuation rate due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. Tagawa, ST., Balar, AV., Petrylak, DP., et al.[2022]

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 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]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, received accelerated approval in 2021 for treating locally advanced and metastatic urothelial carcinoma after prior chemotherapy, showing promising efficacy and safety in clinical trials.

Despite its effectiveness, responses to sacituzumab govitecan are not universal, highlighting the importance of understanding resistance mechanisms and identifying predictive biomarkers to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan. Fontes, MS., Vargas Pivato de Almeida, D., Cavalin, C., et al.[2023]

In a study of 38 patients with invasive bladder cancer, concurrent radiotherapy and panitumumab after chemotherapy resulted in a low rate of severe toxicity (16%), comparable to historical rates for cisplatin and radiotherapy.

The treatment achieved a high complete remission rate of 94%, with promising bladder preservation outcomes, suggesting that this approach could be a viable alternative for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. Fransen van de Putte, EE., Pos, F., Doodeman, B., et al.[2019]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022]

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

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. [2022]

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. England pubmed.ncbi.nlm.nih.gov

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan. [2023]

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

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. [2019]

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

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023]