Sacituzumab Govitecan-hziy for Urothelial Cancer

(TROPiCS-04 Trial)

No longer recruiting at 303 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must be taking: Anti PD-1/PD-L1 therapy

Must not be taking: Monoclonal antibodies, Topoisomerase inhibitors

Disqualifiers: Pregnancy, Active cardiac 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 3.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of a new treatment, sacituzumab govitecan-hziy (an antibody-drug conjugate), in helping individuals with advanced bladder cancer (urothelial cancer) live longer compared to standard treatments. Participants will receive either the new treatment or a standard chemotherapy option selected by their doctor. The trial seeks individuals with advanced bladder cancer that has returned or worsened after previous treatments, including specific chemotherapy and immunotherapy drugs. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

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, you cannot have had certain cancer treatments recently, like chemotherapy or radiation, within 2-4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that sacituzumab govitecan-hziy has been tested in patients with advanced bladder cancer. Studies indicate that it is generally well-tolerated, with common side effects such as low blood cell counts, tiredness, and diarrhea, similar to those of other cancer treatments.

An independent committee regularly reviewed safety data during these studies to ensure patient safety. The FDA granted sacituzumab govitecan-hziy fast-track approval for use in advanced bladder cancer, suggesting a favorable balance between its benefits and risks. ^{1 2 3 4 5}

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

Unlike the standard treatments for urothelial cancer, which include chemotherapy drugs like paclitaxel, docetaxel, and vinflunine, sacituzumab govitecan-hziy offers a novel approach by combining an antibody with a chemotherapy agent. This treatment is unique because it targets a protein called Trop-2, which is often found at high levels in cancer cells, delivering chemotherapy directly to the tumor. Researchers are excited about this innovative mechanism of action, as it has the potential to be more effective and possibly less toxic than traditional chemotherapy options, offering new hope for patients with this type of cancer.

What evidence suggests that sacituzumab govitecan-hziy might be an effective treatment for urothelial cancer?

Research has shown that sacituzumab govitecan-hziy, one of the treatments in this trial, holds promise for treating advanced bladder cancer. In one study, patients using this drug lived for a median of 13.5 months, offering hope for those who have tried other treatments. Another study found that about 11% of patients experienced their cancer shrinking or remaining stable. However, side effects included a decrease in white blood cells, increasing the risk of infections. These findings suggest that sacituzumab govitecan-hziy could be a valuable option for patients with advanced bladder cancer, especially those with limited treatment options. Participants in this trial may receive sacituzumab govitecan-hziy or a treatment of the physician's choice, which includes standard care options like paclitaxel, docetaxel, or vinflunine. ^{1 3 6 7 8}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for adults with advanced urothelial cancer that's spread or can't be surgically removed. They must have already tried a platinum-based treatment and immunotherapy, have good organ function, not be pregnant or breastfeeding, and agree to use birth control. People who've had certain other treatments or health conditions like active infections, second cancers, heart problems, or poor hearing are excluded.

Inclusion Criteria

I am eligible for Docetaxel based on my liver function tests.

I was treated with carboplatin for advanced cancer because I couldn't take cisplatin.

I agree to use birth control.

Exclusion Criteria

I am allergic or cannot tolerate certain cancer drugs.

I have active Hepatitis B or C.

Have other concurrent medical or psychiatric conditions that may confound study interpretation or prevent completion of study procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab govitecan-hziy or treatment of physician's choice in 21-day cycles

Up to 3.5 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan-hziy

Trial Overview The study tests Sacituzumab Govitecan-hziy against the physician's choice of Vinflunine, Paclitaxel, or Docetaxel in patients with advanced urothelial cancer. The main goal is to see if Sacituzumab Govitecan-hziy helps patients live longer compared to standard treatments.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan-hziy Experimental Treatment 1 Intervention

Participants will receive 10 mg/kg of sacituzumab govitecan-hziy intravenously on Day 1 and Day 8 of 21-day cycles.

Group II: Treatment of Physician's Choice Active Control 3 Interventions

Participants will have the choice of receiving paclitaxel, docetaxel, or vinflunine at standard of care (SOC) doses of 175, 75, and 320 mg/m\^2 respectively, every 3 weeks on Day 1 of 21-day cycles.

Sacituzumab Govitecan-hziy 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
• Metastatic urothelial cancer
• Metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative 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?

Gilead Sciences

Lead 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

Everest Medicines

Industry Sponsor

Trials

4

Recruited

1,400+

Published Research Related to This Trial

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

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]

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]

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 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., 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]

Citations

1. 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 (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study. J Clin Oncol 37 ...

2. 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 ...

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

Sacituzumab govitecan in advanced urothelial carcinoma At the data cutoff of 8 March 2024, median follow-up was 9.2 months (range 0-33.7 months). A total of 674 (95%) patients discontinued treatment ...

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

Real-world clinical outcomes of sacituzumab govitecan ... In a large real-world cohort, SG after EV resulted in limited efficacy: ORR 11%, mPFS 2.1 months and mOS 6.0 months. Grade 3-4 neutropenia rates were 36%.

5. gilead.com gilead.com/news/news-details/2023/trodelvy-demonstrates-positive-efficacy-treating-both-platinum-ineligible-and-rapidly-progressing-post-platinum-metastatic-urothelial-cancer

Trodelvy® Demonstrates Positive Efficacy Treating Both ... Oral Presentation Highlights Trodelvy Efficacy of 13.5 Months Overall Survival in Patients with Platinum-Ineligible Metastatic UC After Checkpoint Inhibitor ...

6. 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 ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.7_suppl.354

Sacituzumab govitecan (IMMU-132) in patients with ... Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study.

8. 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 ...