Stage II-IIIa Urothelial Cancer Randomizing Pre-operative Nivolumab With or Without Relatlimab

NCT06237920 | Recruiting Phase 2 DMC

• 1 other identifier: M23TRR
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 9

Brief Summary

This is a non-blinded phase 2 trial in Stage II-IIIa urothelial cancer randomizing pre-operative nivolumab with or without relatlimab to assess whether bladder preservation after dual immunotherapy would be a viable treatment option for patients responding to treatment

Conditions

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

Keywords

Nivolumab; Relatlimab

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  Pathological complete response defined as pT0N0 or pTisN0 in all evaluable patients

  Immediately after surgery

Secondary Outcomes (6)

• Drug toxicity

  Immunotherapy-related adverse events will be noted from time of immunotherapy start at day 1 throughout the study, up to 24 weeks after surgery.

• Feasibility of dual immunotherapy

  [Time Frame: From initiation of study drug until surgery, which will take place between day 50-71 after initiation of study drug]

• Tumor tissue biomarkers predicting treatment response

  12 weeks after immunotherapy administration

• Exploring the Immunological effects of immunotherapy on the tumor microenvironment

  21 weeks after the last patient has started treatment

• Event-free survival

  Through study completion, an average of 2 years

Study Arms (2)

Nivolumab

EXPERIMENTAL

1 cycle of intravenous nivolumab on day 1 and 1 cycle of intraveous nivolumab on day 29. Total administration frequency is twice.

Drug: Nivolumab

Nivolumab and relatlimab

EXPERIMENTAL

1 cycle of intravenous nivolumab and relatlimab on day 1 and 1 cycle of intraveous nivolumab and relatlimab on day 29. Total administration frequency is twice.

Drug: Nivolumab; Drug: Relatlimab

Interventions

Nivolumab DRUG

Induction with immune checkpoint blockade nivolumab on day 1. Nivolumab will also be administered on day 29. Response evaluation will be after the last cycle of checkpoint inhibition.

Also known as: Opdivo

Nivolumab; Nivolumab and relatlimab

Relatlimab DRUG

Induction with immune checkpoint blockade nivolumab and relatlimab on day 1. Nivolumab and relatlimab will also be administered on day 29. Response evaluation will be after the last cycle of checkpoint inhibition.

Also known as: BMS-986016

Nivolumab and relatlimab

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 informed consent
• Age ≥ 18 years
• Resectable muscle-invasive UC of the bladder, defined as cT2-4aN0M0 OR cT1-4aN1M0. In cT1N1 patients, lymph node positivity would need to be cytologically or histologically confirmed.
• Surgical resection (cystectomy) is the advised locoregional treatment and is accepted by the subject after consultation with the urologist.
• Patients are either cisplatin ineligible or elect to not undergo cisplatin based neoadjuvant chemotherapy after a balanced discussion of risks and benefits with the treating physician. Cisplatin eligibility is determined based on the Galsky criteria
• World Health Organization (WHO) performance Status 0 or 1.
• Urothelial cancer is the dominant histology (\>50%). Any component of small cell or adenocarcinoma is not allowed.
• Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available.
• Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR\>30 ml/min, AST ≤ 1.5 x ULN, ALT ≤1.5 x ULN, Bilirubin ≤1.5 X ULN
• Negative pregnancy test (βHCG in blood or urine) within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
• Highly effective contraception for female subjects if the risk of conception exists. Female patients of childbearing potential must comply with contraception methods as requested by the study protocol (→ 8.2.1 Pregnancy, contraception and breastfeeding)

You may not qualify if:

• Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included.
• Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
• Previous intravenous systemic therapy or radiotherapy for UC.
• Upper urinary tract disease, unless all disease is planned to be resected in the same surgery as for UBC. This includes non-muscle-invasive disease.
• Prior CTLA-4, LAG3 or PD-1/PD-L1-targeting immunotherapy.
• Known active Human Immunodeficiency Virus infection, or tuberculosis, or other active infection:
• HIV-positive patients are eligible if the following applies:
• No AIDS defining opportunistic infection within the last year and a current CD4 count \>350 cells/uL.
• Received antiretroviral therapy (ART) for at least 4 weeks prior to treatment and continued while enrolled on study
• CD4 counts and viral load are monitored per standard of care by a local health care provider
• In patients with a known history of hepatitis B or hepatitis C infection, Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) should be negative
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events. Examples may include severe pulmonary disease with extensive radiological abnormalities or intestinal disease causing severe diarrhea, not covered by other eligibility criteria, that may obscure colitis.
• Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) will be allowed.
• Use of other investigational drugs before study drug administration.
• Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated \>10%). Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (9)

Rijnstate

Arnhem, Gelderland, 6815AD, Netherlands

NOT YET RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, 6525GA, Netherlands

RECRUITING

NKI-AVL

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

Amsterdam UMC (AUMC)

Amsterdam, North Holland, 1081HV, Netherlands

RECRUITING

Spaarne Gasthuis

Hoofddorp, North Holland, 2143TM, Netherlands

RECRUITING

ISALA

Zwolle, Overijssel, 8025AB, Netherlands

NOT YET RECRUITING

Leiden University Medical Center (LUMC)

Leiden, South Holland, 2333ZA, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, Zuid_Holland, 3015GD, Netherlands

RECRUITING

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

RECRUITING

MeSH Terms

Conditions

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

Interventions

Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Urologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michiel Van der Heijden, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michiel Van der Heijden, PhD

CONTACT

+31205129111; ms.vd.heijden@nki.nl

Hamza Ali, MSc

CONTACT

+31205129111; h.ali@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: February 2, 2024
• Study Start: February 19, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (9)