A phase 2 trial in stage II-IIIa urothelial cancer randomizing pre-operative nivolumab with or without relatlimab - TURANDORELA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Feb 2024 → ongoing

Decision date (initial)

2024-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol-Myers Squibb

External identifiers

EU CT number

2023-507460-39-00

ClinicalTrials.gov

NCT06237920

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Establish efficacy of nivolumab + relatlimab as neo-adjuvant treatment in muscle-invasive and metastatic bladder cancer

Secondary objectives 3

1. Establish feasibility of nivolumab + relatlimab as neoadjuvant treatment in MIBC
2. Establish additional measures of clinical activity for nivolumab + relatlimab and nivolumab alone
3. Describe safety of nivolumab + relatlimab as neoadjuvant treatment in MIBC

Conditions and MedDRA coding

Adult patients with resectable muscle-invasive urothelial cancer of the bladder, defined as stage II and IIIa UC, who have not yet undergone systemic therapy for UBC.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Willing and able to provide informed consent
2. 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)
3. Age ≥ 18 years
4. Resectable muscle-invasive urothelial cancer of the bladder, defined as cT2-4aN0M0 OR cT1-4aN1M0. Note: in cT1N1 patients, lymph node positivity would need to be cytologically or histologically confirmed
5. 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
6. World Health Organization (WHO) performance Status 0 or 1
7. Urothelial cancer is the dominant histology (>50%). Any component of small cell of adenocarcinoma is not allowed
8. Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available.
9. Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR>30 ml/min, AST ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN
10. Negative pregnancy test (βHCG in blood or urine) within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
11. Surgical resection (cystectomy) is the advised locoregional treatment and is accepted by the subject after consultation with the urologist.

Exclusion criteria 14

1. 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.
2. Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
3. Previous intravenous systemic therapy or radiotherapy for Urothelial cancer.
4. Upper urinary tract disease, unless all disease is planned to be resected in the same surgery as for Urothelial bladder cancer. This includes non-muscle-invasive disease.
5. Prior CTLA-4, LAG3 or PD-1/PD-L1-targeting immunotherapy.
6. 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
7. 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.
8. 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.
9. Use of other investigational drugs before study drug administration
10. 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.
11. Pregnant and lactating female patients.
12. Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
13. Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
14. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias and unstable angina

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathological complete response (pCR), defined as pT0N0 or pTisN0, at cystectomy

Secondary endpoints 3

1. 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.
2. Overall Survival. Event-Free Survival; events are defined as: - Disease progression precluding surgery - Disease recurrence outside the urinary tract (distant metastases, pelvic recurrence) - Muscle invasive recurrence in the bladder or distal ureters - Switch to other treatments directed at systemic urothelial cancer
3. Immune-related adverse events (irAE) according to CTCAE 5.0 criteria

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Department of Biometrics

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Department of Biometrics

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications