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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if sacituzumab govitecan can enhance the effectiveness of surgery for individuals with muscle invasive bladder cancer that has not spread. Sacituzumab govitecan is a targeted therapy that binds to specific receptors on cancer cells, delivering a chemotherapy drug directly to them. The trial seeks participants with muscle invasive bladder cancer confined to the pelvic area who cannot or choose not to take cisplatin, a common chemotherapy drug. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that sacituzumab govitecan is likely to be safe for humans?

Research has shown that sacituzumab govitecan has undergone safety testing in several studies. One study found that most patients tolerated this treatment well. Some experienced side effects, but these were usually manageable. Another study confirmed that the side effects were not too severe for most patients. The FDA has approved the treatment for use in advanced bladder cancer, indicating it has passed important safety checks. Overall, sacituzumab govitecan appears safe for humans based on current data, but discussing possible side effects with a doctor is always advisable. ^{1 2 3 4 5}

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

Sacituzumab govitecan is unique because it combines an antibody with chemotherapy, specifically targeting a protein called Trop-2, which is often found in high levels on bladder cancer cells. This targeted approach allows the drug to deliver chemotherapy directly to the cancer cells, potentially increasing effectiveness while minimizing damage to healthy cells. Unlike traditional treatments like cisplatin-based chemotherapy, which can have significant side effects, sacituzumab govitecan offers a more focused attack on the cancer, which is why researchers are excited about its potential to improve outcomes for patients with bladder cancer.

What evidence suggests that sacituzumab govitecan might be an effective treatment for bladder cancer?

Research has shown that sacituzumab govitecan, the treatment under study in this trial, may effectively treat advanced bladder cancer. This treatment uses a special antibody to locate cancer cells and a chemotherapy drug to destroy them. Studies have found that it can produce significant responses in patients with advanced bladder cancer. However, in some cases, it did not significantly improve overall survival or delay disease progression compared to standard chemotherapy. Despite this, its ability to target specific molecules on cancer cells offers a new approach to treating bladder cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Petros Grivas

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00015-8/fulltext

Sacituzumab govitecan in advanced urothelial carcinoma Sacituzumab govitecan (SG), a Trop-2-directed antibody–drug conjugate, demonstrated efficacy and manageable toxicity in the phase II ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03547973

NCT03547973 | Study of Sacituzumab Govitecan in ... The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12173038/

Real-world clinical outcomes of sacituzumab govitecan ... Sacituzumab govitecan (SG) is an antibody–drug conjugate associated with clinically meaningful responses as advanced-line treatment of metastatic urothelial ...

4. onclive.com onclive.com/view/sacituzumab-govitecan-does-not-significantly-improve-os-in-pretreated-urothelial-carcinoma

Sacituzumab Govitecan Does Not Significantly Improve OS ... Sacituzumab govitecan did not significantly improve OS or PFS over chemotherapy in advanced urothelial carcinoma patients. The antibody-drug ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.03489

TROPHY-U-01: A Phase II Open-Label Study of ... Sacituzumab govitecan (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01631552

Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults ... The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8315301/

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab ... Sacituzumab govitecan (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

8. esmoopen.com esmoopen.com/article/S2059-7029(25)01174-3/fulltext

Real-world clinical outcomes of sacituzumab govitecan ... Highlights. •. There are limited data regarding outcomes of SG in patients with urothelial cancer previously treated with EV.

9. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer

FDA grants accelerated approval for sacituzumab govitecan FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer ... Efficacy and safety were evaluated in TROPHY (IMMU-132 ...