Combination Therapy for Bladder Cancer

(NeoSTOP-IT Trial)

Recruiting at 1 trial location

Overseen By Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Upper tract carcinoma, Autoimmune, Transplant, others

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

Compensation: Varies

Number of Visits: 21

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of drugs, including gemcitabine, cisplatin, and cemiplimab (an immunotherapy drug), with or without fianlimab (an experimental treatment), can effectively treat bladder cancer. Participants will receive one of two treatment plans to identify which combination works best. The trial seeks adults with bladder cancer that has invaded the muscle but has not spread to other parts of the body (no metastatic disease). It suits those who have not undergone certain cancer treatments and are willing to undergo specific procedures during the trial. 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, you cannot participate if you are on certain treatments like systemic steroids or investigational agents within 4 weeks of starting the trial.

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

Research shows that using gemcitabine with cisplatin effectively treats advanced bladder cancer. This combination is generally well-tolerated, with up to 66% of patients responding positively. Studies have also tested adding cemiplimab to these drugs. Early results suggest cemiplimab is usually safe, though some patients may experience fatigue or nausea.

The trial is also evaluating the addition of fianlimab. Fianlimab is a newer drug, and while less information is available, tests in other cancers suggest it is usually well-tolerated. However, it can cause side effects like skin rash or low blood cell counts.

This trial is in a middle phase, indicating the treatment has already passed basic safety tests. While risks remain, this phase aims to gather more detailed safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine standard chemotherapy drugs, Gemcitabine and Cisplatin, with innovative immunotherapies, Cemiplimab and Fianlimab. Cemiplimab is a PD-1 inhibitor that boosts the immune system's ability to attack cancer cells, while Fianlimab targets a different checkpoint, LAG-3, which helps further enhance the immune response against bladder cancer. This dual checkpoint blockade approach is unique and promising because it could potentially improve treatment effectiveness by enabling the immune system to better recognize and fight cancer cells compared to traditional treatments alone.

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

Studies have shown that combining gemcitabine and cisplatin can effectively treat advanced bladder cancer, with up to 66% of patients responding well. This combination is generally easy for patients to tolerate. In this trial, one group of participants will receive gemcitabine, cisplatin, and cemiplimab, a treatment that helps the immune system find and attack cancer cells, potentially enhancing effectiveness. Another group will receive gemcitabine, cisplatin, cemiplimab, and fianlimab, which blocks a protein called LAG-3, possibly further strengthening the immune response. These combinations aim to improve treatment outcomes for people with bladder cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Alexander Z Wei, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

Adults with localized muscle-invasive bladder cancer who can undergo tumor removal and chemotherapy. Participants must be able to receive cisplatin, have no prior treatments for their condition, and not have any autoimmune diseases or conditions that could interfere with the study.

Inclusion Criteria

Life expectancy > 12 months

I am eligible to receive cisplatin treatment.

My bladder cancer is invasive but hasn't spread beyond my bladder.

Exclusion Criteria

I have had radiation therapy for bladder cancer before.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I am currently being treated for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 4 cycles of gemcitabine, cisplatin, and cemiplimab with or without fianlimab, followed by TURBT and imaging

12 weeks

8 visits (in-person)

Recovery

Participants have a recovery period between neoadjuvant treatment and cystoscopy/TURBT

4 weeks

Adjuvant Treatment

Participants with a complete response continue maintenance cemiplimab or cemiplimab/fianlimab for 13 more cycles with imaging every 3 months

39 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Cisplatin
• Fianlimab
• Gemcitabine

Trial Overview The trial is testing if adding cemiplimab (an immune therapy) to standard chemo (gemcitabine/cisplatin) improves treatment outcomes in bladder cancer, with some patients also receiving fianlimab. It's a randomized study where participants are chosen by chance for different treatment combinations.

How Is the Trial Designed?

Group I: Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab Experimental Treatment 4 Interventions

* Gemcitabine 1000 mg/m2 IV (days 1 and 8 of 21 day cycle for 4 cycles) * Cisplatin 70 mg/m2 IV (day 1 of 21 day cycle for 4 cycles) or renally-dosed split-dose cisplatin 35 m/m2 IV (day 1 and 8 of 21 day cycle for 4 cycles ) * Cemiplimab (REGN 2810) 350mg IV every 3 weeks (4 cycles) * Fianlimab (REGN3767) 1600mg IV every 3 weeks (4 cycles)

Group II: Group 1: Gemcitabine/Cisplatin/Cemiplimab Experimental Treatment 3 Interventions

* Gemcitabine 1000 mg/m\^2 IV (days 1 and 8 of 21 day for 4 cycles) * Cisplatin 70 mg/m\^2 IV (day 1 of 21 day cycle for 4 cycles) or renally-dosed split-dose -cisplatin 35 m/m\^2 IV (day 1 and 8 of 21 day cycle for 4 cycles) * Cemiplimab (REGN 2810) 350 mg IV every 3 weeks (17 cycles)

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

The combination of gemcitabine and carboplatin shows a promising overall response rate of 60% in treating transitional cell carcinoma of the bladder, making it a potential alternative for patients who cannot tolerate cisplatin due to renal impairment or other comorbidities.

Given the high chemosensitivity of transitional cell carcinoma, this new treatment combination warrants further investigation in future phase III trials to confirm its efficacy and safety in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin in advanced urothelial cancer. Carles, J., Nogué, M.[2022]

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

The sequential treatment of gemcitabine and cisplatin followed by docetaxel showed a promising objective response rate of 55.2% in 38 patients with advanced urothelial carcinoma, indicating its efficacy as a first-line therapy.

The treatment was generally well tolerated, with manageable side effects; although 27% experienced severe neutropenia during the GP regimen, there were no toxic deaths reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. Boukovinas, I., Androulakis, N., Vamvakas, L., et al.[2022]

Atezolizumab has been approved by the FDA as a treatment for advanced bladder cancer, specifically for patients who cannot receive cisplatin chemotherapy.

This approval provides a potentially more effective treatment option compared to carboplatin-based chemotherapy, particularly for frail and elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

Cisplatin-based regimens, particularly the M-VAC combination therapy, significantly improve complete response rates and overall survival in patients with advanced and metastatic bladder cancer compared to single-agent cisplatin.

For patients ineligible for cisplatin due to health issues, alternative therapies like paclitaxel, gemcitabine, and carboplatin have shown benefits, while new targeted therapies require further research to establish their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review. Sio, TT., Ko, J., Gudena, VK., et al.[2014]

The combination of paclitaxel, cisplatin, and gemcitabine demonstrated a high overall response rate of 77.6% in 61 patients with advanced transitional-cell carcinoma, indicating strong antitumor activity.

The recommended doses for further studies were established as 80 mg/m² of paclitaxel and 1,000 mg/m² of gemcitabine, with manageable toxicity, although significant side effects like grade 3 neutropenia were observed in 55% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. Bellmunt, J., Guillem, V., Paz-Ares, L., et al.[2022]

The gemcitabine and cisplatin (CG) combination has emerged as the new standard of care for metastatic bladder carcinoma, showing similar effectiveness to the previous standard M-VAC regimen but with less toxicity.

Novel treatments like pemetrexed and vinflunine are showing promise in clinical trials, with pemetrexed demonstrating a 28% response rate and vinflunine providing an 18% response rate in pretreated patients, indicating potential for improved outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of metastatic bladder carcinoma. Iaffaioli, RV., Milano, A., Caponigro, F.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS882

A phase 2, randomized, open-label study of gemcitabine ... Genitourinary Cancer—Kidney and Bladder May 2023. A phase II study of toripalimab combined with gemcitabine-cisplatin as neoadjuvant therapy ...

2. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-bladder-cancer/160097-aua-2025-neostop-it-a-phase-2-randomized-open-label-study-of-gemcitabine-cisplatin-plus-cemiplimab-regn2810-anti-pd-1-with-or-without-fianlimab-regn3767-anti-lag-3-for-organ-preservation-in-patients-with-localized-muscle-invasive-bladder-cancer.html

AUA 2025: NeoSTOP-IT: A Phase 2, Randomized, Open- ... A phase 2, randomized, open-label study of gemcitabine/cisplatin plus cemiplimab (REGN2810, anti-PD-1) with or without fianlimab (REGN3767, anti-LAG-3) for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06571708

Study Details | NCT06571708 | Gemcitabine/Cisplatin Plus ... The goal of this clinical trial is to learn if gemcitabine/cisplatin plus cemiplimab with or without fianlimab works to treat bladder cancer in adults.

4. withpower.com withpower.com/trial/phase-2-muscle-invasive-bladder-carcinoma-10-2024-9af68

Combination Therapy for Bladder Cancer (NeoSTOP-IT Trial) Research shows that combining gemcitabine with cisplatin is effective for treating advanced bladder cancer, with response rates up to 66% and good tolerability.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12214084/

Neoadjuvant treatment patterns and biomarker selection in ... A real-world study reviewed data on neoadjuvant treatment of MIBC patients with either DV monotherapy or in combination with ICIs. With a median ...