Sacituzumab Govitecan-hziy for Urothelial Cancer

(TROPiCS-04 Trial)

Recruiting at 247 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

696 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to assess overall survival (OS) with sacituzumab govitecan-hziy in comparison with treatment of physician's choice (TPC) in participants with metastatic or locally advanced unresectable urothelial cancer (UC).

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.

What data supports the effectiveness of the drug Sacituzumab Govitecan-hziy for treating urothelial cancer?

Sacituzumab govitecan has shown promising results in patients with metastatic urothelial carcinoma, especially those who have not responded to other treatments, with preliminary studies indicating it can help shrink tumors. It has also been approved for treating a type of breast cancer, which suggests its potential effectiveness in other cancers. ^{1 2 3 4 5}

What safety data exists for Sacituzumab Govitecan-hziy?

Sacituzumab Govitecan-hziy, also known as Trodelvy, has been associated with side effects like neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). These side effects often occur within 30 days of starting treatment, and some may lead to hospitalization, especially in males. ^{1 2 3 4 6}

What makes the drug sacituzumab govitecan-hziy unique for treating urothelial cancer?

Sacituzumab govitecan-hziy is unique because it is an antibody-drug conjugate that specifically targets Trop-2, a protein often found in high amounts on cancer cells, and delivers SN-38, a powerful cancer-fighting agent, directly to the tumor. This targeted approach allows for higher concentrations of the drug to reach the cancer cells, potentially improving effectiveness compared to standard treatments. ^{1 2 3 4 7}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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.

Creatinine clearance ≥30 mL/min.

Exclusion Criteria

I am allergic or cannot tolerate certain cancer drugs.

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

I have active Hepatitis B or C.

Timeline

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

Treatment Details

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.

Participant Groups

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+

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]

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 (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]

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]

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]

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

Sacituzumab Govitecan: First Approval. [2021]

5. United States 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. [2018]

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

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

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

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]