Health TrialsbyHealthPanel

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

ConditionsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesMale Urogenital DiseasesUrinary Bladder NeoplasmAntineoplastics Toxicity
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Netherlands Cancer Institute

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

Treatment groups

90 Participants
are divided into 2 treatment groups
Group A: NivolumabExperimental treatment 1 intervention
Group B: Nivolumab and relatlimabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Pathological complete response

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

Time frame
Immediately after surgery

Secondary outcomes

1

Drug toxicity

Safety in terms of immunotherapy-related adverse events according to CTCAE 5.0 criteria

Time frame
Immunotherapy-related adverse events will be noted from time of immunotherapy start at day 1 throughout the study, up to 24 weeks after surgery.
2

Feasibility of dual immunotherapy

Percentage of patients that completes cystectomy within 12 weeks of start of treatment. Patients who elect to not undergo surgery or have a delay due to logistical reasons not related to study treatment will be excluded from this analysis.

Time frame
[Time Frame: From initiation of study drug until surgery, which will take place between day 50-71 after initiation of study drug]
3

Tumor tissue biomarkers predicting treatment response

PD-L1 expression of tumor tissue (obtained pre-treatment) will be determined using immunohistochemistry of tissue slides. For PD-L1, tumor proportion score (TPS) will be determined. Pathological complete response will be related to PD-L1 expression

Time frame
12 weeks after immunotherapy administration
4

Exploring the Immunological effects of immunotherapy on the tumor microenvironment

RNA sequencing and multiplex immunofluorescence will be carried out on TUR and cystectomy tumor tissue. Methods may include RNA expression profiling and multiplex immunofluorescence.

Time frame
21 weeks after the last patient has started treatment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

The Netherlands Cancer Institute

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
Apply now