Sacituzumab Govitecan + Nivolumab for Bladder Cancer

Overseen By University of California Irvine Medical

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Active malignancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 15 cycles

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, Sacituzumab Govitecan (a targeted therapy) and Nivolumab (an immunotherapy drug), to determine if they prevent bladder cancer from returning after surgery. It targets individuals who have had muscle-invasive urothelial carcinoma (a type of bladder cancer) and are at high risk of recurrence. Participants should show no signs of cancer on recent scans and have undergone surgery to remove the cancer, yet still face a high chance of recurrence. The trial aims to offer a new option for those in this challenging situation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on high-dose corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of Sacituzumab Govitecan and Nivolumab is generally well-tolerated. Sacituzumab Govitecan, already approved for advanced bladder cancer, has been used safely in patients. Common side effects include tiredness and nausea, but these are often manageable.

Nivolumab, the other component of this treatment, helps maintain patients' quality of life, meaning it usually doesn't worsen daily activities. Some individuals might experience mild side effects like tiredness or a skin rash, but these are generally mild.

Overall, this combination has shown promise without a major increase in serious side effects. Evidence from previous studies suggests that the treatment is relatively safe for those considering this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sacituzumab Govitecan and Nivolumab for bladder cancer because it offers a novel approach compared to standard treatments like chemotherapy and immune checkpoint inhibitors alone. Sacituzumab Govitecan is an antibody-drug conjugate that specifically targets and delivers chemotherapy directly to cancer cells, potentially increasing effectiveness while reducing side effects. When paired with Nivolumab, an immunotherapy that helps the immune system better recognize and attack cancer cells, this combo could enhance the overall response in patients. This targeted approach and synergistic effect are why there's a buzz about these treatments in the medical community.

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

Research has shown that Sacituzumab Govitecan, which targets the protein Trop-2, yields promising results in treating various solid tumors, including bladder cancer. Specifically, the TROPHY-U-01 study found early positive effects in treating metastatic urothelial carcinoma, a type of bladder cancer that has spread. Nivolumab, an immune therapy, has benefited patients without reducing their quality of life. In this trial, participants will receive a combination of Sacituzumab Govitecan and Nivolumab, aiming to leverage the strengths of both drugs, potentially offering a more effective treatment for high-risk bladder cancer. This combination is under study to determine if it can reduce the chance of cancer recurrence after surgery. ^{1 2 4 5 6}

Who Is on the Research Team?

Nataliya Mar, MD

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with muscle-invasive urothelial carcinoma, which includes cancers of the bladder, ureter, or upper tract. It's specifically for those at high risk of cancer coming back after surgery meant to cure them.

Inclusion Criteria

My cancer started in the bladder, ureter, or renal pelvis and is not small cell carcinoma.

Radiographic disease-free status as determined by imaging within 28 days of C1 D1 of study treatment

I have had platinum-based chemo before surgery and cannot or choose not to have platinum chemotherapy now.

Exclusion Criteria

I haven't had any cancer except for certain types in the last 3 years.

I have or might have an autoimmune disease.

I have had radiation therapy for urinary cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with Sacituzumab Govitecan and Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles

15 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Sacituzumab Govitecan

Trial Overview The study is testing a combination therapy using two drugs: Sacituzumab Govitecan and Nivolumab. As it's a phase 2 single-arm study, all participants will receive this combo treatment to see how effective it is in preventing cancer recurrence.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan PLUS Nivolumab Experimental Treatment 2 Interventions

Patients eligible for this study treatment will receive combination therapy with Sacituzumab Govitecan with Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

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]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

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 (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]

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 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, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., 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]

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 (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

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

Sacituzumab govitecan in advanced urothelial carcinoma We report the results from final analysis of the global open-label randomized phase III TROPiCS-04 study (NCT04527991) in pretreated aUC.

3. onclive.com onclive.com/view/qol-benefits-with-nivolumab-challenges-with-sacituzumab-govitecan-characterize-bladder-cancer-management-updates

QOL Benefits With Nivolumab, Challenges ... “These results consolidate the role of this regimen by showing that it does not lead to any declining QOL, and it does improve outcomes,” said ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01720

TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab ... Sacituzumab govitecan (SG) is a Trop-2–directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0923753425000158

TROPiCS-04, a phase III randomized trial Sacituzumab govitecan (SG), an antibody directed to Trophoblast cell surface antigen 2 (Trop-2), has shown notable antitumor activity in various solid tumors.19 ...

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 ...