Gemcitabine/Cisplatin Plus Cemiplimab With or Without Fianlimab in Localized Muscle-invasive Bladder Cancer (NeoSTOP-IT)

NCT06571708 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAV3927
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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. The main question it aims to answer is: Can gemcitabine, cisplatin, and cemiplimab with or without fianlimab treat bladder cancer? Participants will be randomly selected (like the loss of a coin) to treatment with gemcitabine, cisplatin, cemiplimab, and fianlimab or gemcitabine, cisplatin, and cemiplimab. Participants will:

• Undergo transurethral resection of bladder tumor (TURBT) followed by the start of treatment, receive 4 cycles of treatment (21 day cycles)
• After 4 cycles of treatment, patients will undergo repeat maximal TURBT with imaging
• Participants with a complete response will continue maintenance cemiplimab or cemiplimab/fianlimab for 13 more cycles with imaging every 3 months
• Participants without a complete clinical response will undergo cystectomy (bladder surgery).

Conditions

Bladder Cancer; Muscle-Invasive Bladder Carcinoma

Keywords

Urothelial Predominant Histology

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response

  Rate of clinical complete response after 4 cycles of neoadjuvant chemoimmunotherapy. Complete clinical response will be defined as: * No high-grade malignancy on repeat TURBT * No malignant cells on urine cytology * No definitive evidence of invasive local or metastatic disease on cross-sectional imaging (CT chest, abdomen, and pelvis with contrast or, if renal dysfunction, MRI with contrast) Cytoscopy and imaging should occur within 4 weeks of end of neoadjuvant therapy.

  16 weeks

Secondary Outcomes (4)

• Number of Adverse Events

  30 days after last dose of treatment, up to 56 weeks

• Bladder-intact survival

  Up to 5 years

• Recurrence-free survival

  Up to 5 years

• Overall survival

  Up to 5 years

Study Arms (2)

Group 1: Gemcitabine/Cisplatin/Cemiplimab

EXPERIMENTAL

* 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)

Drug: Gemcitabine; Drug: Cisplatin; Drug: Cemiplimab

Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab

EXPERIMENTAL

* 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)

Drug: Gemcitabine; Drug: Cisplatin; Drug: Cemiplimab; Drug: Fianlimab

Interventions

Gemcitabine DRUG

Gemcitabine 1000 mg/m\^2 IV

Group 1: Gemcitabine/Cisplatin/Cemiplimab; Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab

Cisplatin DRUG

Cisplatin 70 mg/m\^2 IV or renally-dosed split-dose cisplatin 35 m/m\^2 IV

Group 1: Gemcitabine/Cisplatin/Cemiplimab; Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab

Cemiplimab DRUG

Cemiplimab 350mg IV

Also known as: REGN 2810

Group 1: Gemcitabine/Cisplatin/Cemiplimab; Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab

Fianlimab DRUG

Fianlimab 1600mg IV

Also known as: REGN3767

Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent for the trial.
• Age ≥18 years of age on day of signing informed consent.
• Life expectancy \> 12 months.
• Performance status of 0-1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder defined as T2-T3, N0, M0 stage. Mixed histology is permitted if there is a urothelial component. Upper tract disease in not permitted.
• Prior Bacillus Calmette-Guerin (BCG) or other intravesical treatment of non-muscle invasive bladder cancer is permitted if completed at least 6 weeks prior to initiating study treatment. Only one course (includes induction + maintenance) of BCG or intravesical therapy is permitted.
• No metastatic disease based on cross-sectional imaging.
• Considered cisplatin eligible based on protocol specified criteria.
• Not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.
• Agree to pre- and post-treatment TURBT as well as surveillance with cystoscopies, cross-sectional imaging, and urine cytology unless medically contraindicated in the opinion of the treating physician, and discussed with the principal investigator

You may not qualify if:

• Concurrent upper urinary tract (i.e., ureter, renal pelvis) invasive urothelial carcinoma. (NOTE: Patients with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post- treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible).
• Received prior immune checkpoint inhibitors (including anti-PD-1, anti-PD-L1, anti-CTLA4, anti-LAG-3 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways ), as well as cellular vaccines, cellular therapies, or systemic oncolytic virus therapy.
• Received bladder-directed radiation therapy previously for bladder cancer.
• Received prior systemic chemotherapy for muscle-invasive bladder cancer.
• Receiving any other investigational agents concurrently or within 4 weeks of start of treatment.
• Had a solid organ or hematologic transplant.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose greater than 10mg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Has a history of myocarditis.
• Patients with another active second malignancy other than non-melanoma skin cancers.
• Has a known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis.
• Has an active infection requiring systemic therapy.
• History or current evidence of significant (Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
• Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection.

Sponsors & Collaborators

• Columbia University: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Columbia University Irving Medical Center/ New York Presbyterian Hospital

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Gemcitabine; Cisplatin; cemiplimab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Alexander Z Wei, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Z Wei, MD

CONTACT

212-305-5874; aw3056@cumc.columbia.edu

Nurse Navigator

CONTACT

212-305-5098; cancerclinicaltrials@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine at the Columbia University Medical Center

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 26, 2024
• Study Start: August 14, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 2, 2025

Record last verified: 2025-08

Locations

US (1)