A Study of Gemcitabine/Cisplatin Plus Cemiplimab (REGN2810, Anti-PD-1) With or Without Fianlimab (REGN3767, Anti-LAG-3) in Patients With Localized Muscle-invasive Bladder Cancer (NeoSTOP-IT)

Registration Number
NCT06571708
Lead Sponsor
Columbia University
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?
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Detailed Description

This is a phase 2, open-label, randomized trial with continuous toxicity monitoring to ensure safety using Bayesian toxicity monitoring, which will evaluate treatment with doublet platinum-based chemotherapy (gemcitabine and cisplatin) plus cemiplimab (REGN2810) with or without fianlimab (REGN3767) for localized muscle-invasive bladder cancer (MIBC). Partici...

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
36
Inclusion Criteria
  • 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 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
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Exclusion Criteria
  • 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.
  • Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment
  • 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 (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 HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection.
  • Is pregnant or is a breastfeeding woman.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 2: Gemcitabine/Cisplatin/Cemiplimab/FianlimabFianlimab* 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 1: Gemcitabine/Cisplatin/CemiplimabGemcitabine* 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)
Group 1: Gemcitabine/Cisplatin/CemiplimabCisplatin* 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)
Group 1: Gemcitabine/Cisplatin/CemiplimabCemiplimab* 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)
Group 2: Gemcitabine/Cisplatin/Cemiplimab/FianlimabGemcitabine* 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 2: Gemcitabine/Cisplatin/Cemiplimab/FianlimabCisplatin* 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 2: Gemcitabine/Cisplatin/Cemiplimab/FianlimabCemiplimab* 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)
Primary Outcome Measures
NameTimeMethod
Clinical Complete Response16 weeks

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
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Secondary Outcome Measures
NameTimeMethod
Overall survivalUp to 5 years

Overall survival is defined as the time from start of treatment until death.

Recurrence-free survivalUp to 5 years

Recurrence-free survival is defined as the time from start of treatment until disease recurrence or death. Recurrence-survival will only be measured in patients who achieve a clinical complete response.

Bladder-intact survivalUp to 5 years

Bladder-intact survival is defined as the time from start of treatment until cystectomy or death.

Number of Adverse Events30 days after last dose of treatment, up to 56 weeks

Defined as the occurrence of any adverse event (AE) related to the investigational drugs at any point on treatment until 30 days after the last dose of treatment. AEs as evaluated per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Trial Locations

Locations (1)

Columbia University Irving Medical Center

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New York, New York, United States

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