CETRELIMAB for Muscle-invasive bladder cancer (MIBC) | Bladder cancer

Inclusion criteria

• {"criterion_text":"- 1.\tWritten informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study.\n- 10. Willingness to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of erdafitinib and/or 150 days after the last dose of cetrelimab, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriateprecautions to avoid pregnancy (with at least 99% certainty) from screening through 90 days after the last dose of erdafitinib and/or 150 days after the last dose of cetrelimab (Acceptable contraception is defined in Appendix 8). A WOCBP is a female who 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (has had at least menses at any time preceding 12 consecutive months). Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of aamenorrhea) are eligible.\n- 2. Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal TURBT performed no later than 3 months prior to start the screening visit.\n- 3. Pure or predominant (≥50%) UC histology as determined at the local site.\n- 4. Age ≥ 18 years.\n- 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n- 6. Decline or ineligible (“unfit”) for cisplatin-based chemotherapy as defined by any one of the following criteria: a. Impaired renal function (glomerular filtration rate [GFR] ≥ 30 but < 60 mL/min). GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. b. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 ≥ Grade 2 hearing loss (assessed per local standard of care). c. CTCAE, Version 5.0 ≥ Grade 2 peripheral neuropathy. d. Any other reason to be ineligible for cisplatin should be consulted with the coordinating PI.\n- 7. Presence of a selected FGFR alteration on analysis of tumour biopsy. Local reports based on validated tests can be accepted (with subsequent confirmation by Central Laboratory). Patients having positive local testing will not have to wait for confirmation to be enrolled. It is required fromall patients to send tumour sample to Central Laboratory to analyse DNA mutations and RNA fusion by Next Generation Sequencing and eCounter, respectively. In case of discrepancies, the local determination will prevail.\n- 8. Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to Cycle 1 Day 1 (medical management allowed): a. Absolute Neutrophil Count (ANC) ≥1.5 x 109/L. b. Platelets ≥100 x 109/L. c. Haemoglobin ≥9 g/dL (5.6 mmol/L). d. International normalized ratio (INR) or Prothrombin time (PT) ≤1.5 x ULN e. Total bilirubin ≤1.5 x ULN except patients with Gilbert Syndrome, who must have a total bilirubin level of <3.0 x ULN. f. ALT and AST ≤2.5 x ULN g. Creatinine clearance ≥30 mL/min. h. Phosphate < Upper Limit of Normal (ULN)\n- 9. No other malignancy (diagnosis within the last 3 years), except for treated non-melanoma skin cancer (basal or squamous), carcinoma in situ of cervix and low risk prostate cancer."}

Exclusion criteria

• {"criterion_text":"- 1. Clinical evidence of N2-N3 tumours or metastatic bladder cancer.\n- 10. Uncontrolled adrenal insufficiency.\n- 11. True positive test results for hepatitis B, or C during screening.\n- 12. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).\n- 13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring medication except for atrial fibrillation that is rate controlled with medication, myocardial infarction within 6 months of Cycle 1 Day 1, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.\n- 14. Known allergy or hypersensitivity to study drug formulations.\n- 15. Known history of allergy to protein-based therapies or a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia).\n- 16. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment (RPED) of any grade.\n- 17. Inability to swallow and retain oral medication.\n- 18. History of calcium and phosphate homeostasis disorder or systemic mineral imbalance.\n- 19. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.\n- 2. Has tumour with any neuroendocrine or small cell component.\n- 20. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.\n- 21. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.\n- 22. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.\n- 23. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 480 ms is excluded.\n- 3. Patients who are not considered fit for cystectomy or reject cystectomy.\n- 4. Patients with co-morbidities that will preclude them from trial intervention.\n- 5. Prior FGFR-targeted or antiPD1/PDL1 systemic therapy.\n- 6. Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than transurethral resection of bladder tumour (TURBT) or biopsies is not permitted. Prior BCG or other intravesical treatment of non-MIBC is permitted if completed at least 6 weeks prior to initiating study treatment.\n- 7. Evidence of UC in upper urinary tracts (ureters or renal pelvis), prostatic urethra,history of previous MIBC or UC not confined to the bladder.\n- 8. Major surgical procedure within 14 days prior to the first dose or still recovering from prior surgery.\n- 9. Severe infection within 4 weeks prior to allocation."}

Primary endpoints

• {"endpoint_text":"- Pathological complete response (pCR)","definition_or_measurement_approach":"Antitumor activity measured as pT0N0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen."}
• {"endpoint_text":"- Pathological downstaging < ypT2","definition_or_measurement_approach":"To assess the percentage of pathological downstaging response < ypT2."}

Secondary endpoints

• {"endpoint_text":"- Rate of pathological downstaging (pDS)","definition_or_measurement_approach":"Defined as pathological TNM less than clinical TNM."}
• {"endpoint_text":"- Event-free Survival rate","definition_or_measurement_approach":"Defined as disease progression, death or any event that prevents the performance of RC, including initiation of any additional therapy prior to RC."}
• {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall survival; no further definition provided in the available record."}
• {"endpoint_text":"- ORR according to RECIST, after neoadjuvant treatment","definition_or_measurement_approach":"Objective Response Rate assessed by RECIST v1.1 in subjects after neoadjuvant treatment (prior to radical cystectomy)."}
• {"endpoint_text":"- Adverse events","definition_or_measurement_approach":"Safety/tolerability assessed by collection of adverse events (no additional measurement detail in available record)."}
• {"endpoint_text":"- Rate of delay of surgery (classed as a delay event if performed > 6 weeks after last dose of treatment)","definition_or_measurement_approach":"Delay event defined as surgery performed > 6 weeks after last dose of treatment."}

Italy

Earliest CTIS Part Ii Submission Date

17-07-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

646

Number Of Sites

3

Number Of Participants

16

Spain

Earliest CTIS Part Ii Submission Date

17-07-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

646

Number Of Sites

10

Number Of Participants

23

France

Earliest CTIS Part Ii Submission Date

17-07-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

646

Number Of Sites

5

Number Of Participants

23

Primary sponsor

Full Name

Grupo Espanol De Oncologia Genitourinaria-Socug

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Contract research organisations

Name

Pivotal S.L.

Responsibilities

sponsorDuties codes: 1,10,12,6,8,9 (various trial services as listed in record)

Third parties

• {"country":"United Kingdom","full_name":"University Of Sheffield","duties_or_roles":"Imaging diagnosis","organisation_type":"Educational Institution"}
• {"country":"Spain","full_name":"Instituto Oncologico Dr. Rosell S.L.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"sponsorDuties codes: 1,10,12,6,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Hospital Universitario 12 De Octubre","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Drug depot","organisation_type":"Pharmaceutical company"}