Pre-Surgery Sacituzumab Govitecan for Bladder Cancer

Overseen By Patrick Panlasigui

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Irinotecan, Topotecan

Disqualifiers: Neuroendocrine histology, Active infection, Hepatitis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 9 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether sacituzumab govitecan given before radical cystectomy works in treating patients with non-urothelial bladder cancer. Sacituzumab govitecan contains a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan before radical cystectomy may make the surgery more effective in patients with muscle invasive bladder cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does exclude those who have had prior systemic anti-cancer therapy within 4 weeks or prior radiation therapy within 2 weeks, and those on medications that interfere with certain enzymes. It's best to discuss your specific medications with the trial team.

Is sacituzumab govitecan generally safe for humans?

Sacituzumab govitecan has been used for treating breast and urothelial cancers, 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 some may lead to hospitalization, especially in males. ^{1 2 3 4 5}

How is the drug sacituzumab govitecan unique for bladder cancer treatment?

Sacituzumab govitecan is unique because it is an antibody-drug conjugate that targets Trop-2, a protein often found in high amounts on cancer cells, and delivers SN-38, a powerful cancer-fighting agent, directly to these cells. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{1 2 4 5 6}

Research Team

Petros Grivas

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with muscle invasive bladder cancer who haven't had major surgery or other cancer treatments recently. They must be fit enough for radical cystectomy, not pregnant or breastfeeding, and willing to use contraception. People with neuroendocrine/small cell histology, another interfering malignancy, significant heart disease, active infections requiring antibiotics, or known allergies to the study drug are excluded.

Inclusion Criteria

Your body has enough infection-fighting cells.

I am not suitable for cisplatin treatment or I have refused it after being advised.

Your bilirubin levels must be within a certain range.

Exclusion Criteria

I do not have another cancer that could affect the study's results.

I have an active hepatitis B or C infection.

I am currently on antibiotics for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan intravenously over 3 hours on days 1 and 8 of each cycle. Treatment repeats every 21 days for 3 cycles.

9 weeks

6 visits (in-person)

Surgery

Participants undergo radical cystectomy and pelvic lymph node dissection within 2-6 weeks after the last dose of treatment.

2-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up at 1-3 months after surgery and then every 3-6 months for 2 years.

2 years

Treatment Details

Interventions

• Sacituzumab Govitecan

Trial Overview The trial is testing Sacituzumab Govitecan given before surgery (radical cystectomy) in patients with non-urothelial bladder cancer. It's a phase II study to see if this targeted therapy that delivers chemotherapy directly to cancer cells can improve surgical outcomes.

Participant Groups

Group I: Treatment (sacituzumab govitecan) Experimental Treatment 3 Interventions

Patients receive sacituzumab govitecan IV over 3 hours on days 1 and 8 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks after last dose, patients undergo radical cystectomy and pelvic lymph node dissection.

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

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer
• Locally advanced or metastatic urothelial cancer (withdrawn)
• Metastatic HR+/HER2- breast cancer

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

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 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]

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]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

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]

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]

References

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

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

2. 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]

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

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

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

Sacituzumab Govitecan: First Approval. [2021]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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