Ipi/Nivo + Sacituzumab Govitecan for Bladder Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Anti-PD-1/PD-L1, Topoisomerase I

Disqualifiers: Pregnancy, Small-cell carcinoma, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for metastatic bladder cancer. Researchers aim to evaluate how well Ipilimumab (Yervoy) and Nivolumab (Opdivo) work with Sacituzumab Govitecan (Trodelvy) to combat cancer that has spread. Participants will receive varying doses to identify the most effective treatment with the fewest side effects. Individuals with metastatic bladder cancer who cannot undergo certain chemotherapy may be suitable for this trial. As a Phase 1 and Phase 2 trial, this research seeks to understand the treatment's effects in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take medications that interfere with certain drug transporters or enzymes, and you must be off high-dose steroids for at least two weeks before starting the trial.

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

Studies have shown that the combination of Ipilimumab, Nivolumab, and Sacituzumab Govitecan is generally well-tolerated by patients. In research involving Sacituzumab Govitecan, about 27-28% of participants with advanced bladder cancer experienced tumor shrinkage. On average, patients lived about 10.5 months after starting treatment.

Research indicates that using these drugs together can cause some side effects, but they are usually manageable. Common side effects include fatigue, nausea, and reduced appetite. These side effects were not severe enough to make most patients discontinue treatment.

Prospective trial participants should discuss potential side effects and benefits with their doctor to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for bladder cancer, which often involves chemotherapy and immune checkpoint inhibitors, the combination of Ipilimumab, Nivolumab, and Sacituzumab Govitecan targets cancer cells in a novel way. Researchers are excited because Sacituzumab Govitecan is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially increasing effectiveness while reducing harm to healthy cells. Additionally, the pairing with Ipilimumab and Nivolumab, both immune checkpoint inhibitors, may enhance the immune system's ability to attack cancer cells. This combination could offer a more tailored and potent approach to treating bladder cancer.

What evidence suggests that this trial's treatments could be effective for metastatic bladder cancer?

Research has shown that Ipilimumab and Nivolumab, two drugs that boost the immune system, can help people with advanced bladder cancer. Studies have found that this combination might be beneficial, especially if other treatments have failed. Sacituzumab Govitecan, another drug that targets cancer cells directly, has shown promise in treating bladder cancer. In this trial, participants will receive a combination of Ipilimumab, Nivolumab, and Sacituzumab Govitecan at various dose levels to evaluate their combined effectiveness. Although the combined effects of these drugs are still under investigation, each has proven effective individually. The aim is that using them together might provide a stronger defense against cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Guru P Sonpavde, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with advanced bladder cancer who can't use cisplatin chemotherapy due to certain health issues. They must have a good performance status, no severe heart disease or active infections, and not be pregnant. Men and women must agree to contraception methods.

Inclusion Criteria

My lab tests show my organs are working well.

Able to understand and give written informed consent

My cancer is a mainly urothelial carcinoma and has spread beyond the bladder.

Exclusion Criteria

I have HIV with a high viral load and take medication that could affect my treatment.

I am taking medication that affects ABCA1 transporter or UGT1A1.

I have stable brain metastases, not on high-dose steroids, and no carcinomatous meningitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Participants receive Ipilimumab and Nivolumab every 3 weeks for 4 cycles, combined with Sacituzumab Govitecan at varying doses

12 weeks

4 visits (in-person)

Treatment Phase II

Participants continue with maintenance Nivolumab and Sacituzumab Govitecan until disease progression or intolerable toxicities

Up to 12 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Radiographic imaging every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Sacituzumab govitecan

Trial Overview

The trial tests Ipilimumab plus Nivolumab (IPI-NIVO) combined with Sacituzumab Govitecan in patients with metastatic bladder cancer. It aims to determine the effectiveness of this drug combination for those ineligible for cisplatin chemotherapy.

How Is the Trial Designed?

Group I: Phase 2: Treatment at Maximum Tolerated Dose (MTD) Experimental Treatment 3 Interventions

Participants will be treated at with Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks plus the maximum tolerated dose of Sacituzumab Govitecan days 1 and 8 every 3 weeks.

Group II: Phase 1 Dose Level 2 Experimental Treatment 3 Interventions

Participants will be treated at dose level 2: Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks. Sacituzumab Govitecan 10 mg/kg IV will be administered days 1 and 8 every 3 weeks.

Group III: Phase 1 Dose Level 1 Experimental Treatment 3 Interventions

Participants will be treated at dose level 1: Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks. Sacituzumab Govitecan 8 mg/kg IV will be administered days 1 and 8 every 3 weeks.

Group IV: Phase 1 Dose Level -1 Experimental Treatment 3 Interventions

If dose reduction is indicated, participants will be treated at dose level -1: Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks. Sacituzumab Govitecan 6 mg/kg IV will be administered days 1 and 8 every 3 weeks

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

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 II trial involving 51 patients with muscle-invasive bladder cancer, the combination of nivolumab and gemcitabine/cisplatin (N+GC) was well tolerated and resulted in a clinical complete response in 59% of patients, indicating its potential effectiveness as a neoadjuvant treatment.

The treatment led to a pathologic complete response in 24% of patients overall and 35% among those who underwent radical cystectomy, suggesting that N+GC can achieve significant tumor reduction before surgery, regardless of the patients' PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. Kim, H., Jeong, BC., Hong, J., et al.[2023]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In a study of 38 patients with invasive bladder cancer, concurrent radiotherapy and panitumumab after chemotherapy resulted in a low rate of severe toxicity (16%), comparable to historical rates for cisplatin and radiotherapy.

The treatment achieved a high complete remission rate of 94%, with promising bladder preservation outcomes, suggesting that this approach could be a viable alternative for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. Fransen van de Putte, EE., Pos, F., Doodeman, B., et al.[2019]

The combination of gemcitabine and irinotecan (Irinogem) showed promising efficacy in treating metastatic bladder cancer, with 8 out of 13 evaluable patients achieving an objective response, including 2 complete responses and 6 partial responses, and a median progression-free survival of 8.78 months.

The treatment was associated with manageable toxicity, with no toxic deaths reported, although some patients experienced significant side effects like neutropenia and diarrhea. However, the study's early closure due to funding issues limits the ability to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. Chaudhary, UB., Verma, N., Keane, T., 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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04863885

Study Details | NCT04863885 | Combination of Ipi/Nivo ...

The purpose of this study is to see how well the study drugs called Ipilimumab plus Nivolumab (IPI-NIVO) work when added to another study drug called ...

2.

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 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11082753/

Nivolumab + Ipilimumab as Immunotherapeutic Boost in ...

These findings suggest that second-/third-line nivolumab plus high-dose ipilimumab may benefit patients with metastatic urothelial carcinoma.

4.

opdivo.com

opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/advanced-untreated-immunotherapy-chemo

Clinical trial results for advanced bladder or urinary tract ...

See how OPDIVO® (nivolumab) plus chemotherapy performed in a clinical trial as a treatment for certain adults with advanced bladder or urinary tract cancer, ...

5.

opdivo.com

opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/advanced-previously-treated-immunotherapy

Previously Treated Advanced Bladder or Urinary Tract ...

See how OPDIVO® (nivolumab) performed in a clinical trial as a treatment for certain adults with previously treated advanced bladder or urinary tract cancer ...

6.

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.

7.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)03573-7/fulltext

1969P Phase I/II study of ipilimumab plus nivolumab ...

Sacituzumab govitecan (SG) demonstrated an objective response rate (ORR) of 28% and median overall survival (OS) of 10.5 months (mo) in metastatic ...

8.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.521

Phase I/II study of ipilimumab plus nivolumab combined ...

Background: Sacituzumab govitecan (SG) demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months ...