Ipi/Nivo + Sacituzumab Govitecan for Bladder Cancer

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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

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 Sacituzumab Govitecan for people who have metastatic bladder cancer.

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.

What data supports the effectiveness of the drug combination Ipi/Nivo + Sacituzumab Govitecan for bladder cancer?

Sacituzumab govitecan has shown preliminary activity in treating metastatic urothelial carcinoma (a type of bladder cancer) in patients who have not responded to other treatments, with some studies indicating it can help when other options are limited. ^{1 2 3 4 5}

Is the combination of Ipi/Nivo and Sacituzumab Govitecan safe for bladder cancer treatment?

The combination of nivolumab (Nivo) and sacituzumab govitecan has been studied in clinical trials for bladder cancer, and these treatments are generally well tolerated. Common side effects of similar treatments include fatigue, low blood cell counts, muscle pain, decreased appetite, and nausea. ^{6 7 8 9 10}

How is the drug combination of Ipi/Nivo and Sacituzumab Govitecan unique for bladder cancer?

This drug combination is unique because it combines immune checkpoint inhibitors (Ipilimumab and Nivolumab) with Sacituzumab Govitecan, an antibody-drug conjugate targeting Trop-2, a protein often found in high levels on bladder cancer cells. This approach aims to enhance the immune response against cancer while delivering a potent chemotherapy agent directly to the tumor. ^{2 3 4 5 11}

Research Team

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Guru P Sonpavde, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

References

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

The role of enfortumab vedotin and sacituzumab govitecan in treatment of advanced bladder cancer. [2022]

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

Sacituzumab Govitecan: First Approval. [2021]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. [2023]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

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

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma. [2023]

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

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. [2022]

11. 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]