INCB24360-901 - Umbrella Study of Various Neoadjuvant Therapies for Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Cisplatin-Ineligible or Refuse Cisplatin Therapy and Undergoing Radical Cystectomy (Optimus).

Studio Clinico

Patologia: Carcinoma della vescica

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II Randomizzato

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Adiuvante/neoadiuvante

Criteri di inclusione: 

• Histologically confirmed transitional cell urothelial carcinoma. Participants with mixed histologies are required to have a dominant (ie, 50% at least) transitional cell pattern.
• Clinical stage T2-T3b, N0, M0 muscle invasive urothelial carcinoma by CT (or MRI) (Stage II-IIIA per AJCC 2018)
• Refuse cisplatin therapy (does not apply in France) or are ineligible for cisplatin therapy per modified Galsky criteria with exclusion of Eastern Cooperative Oncology Group( ECOG) PS 2 participants
• Eligible for radical cystectomy
• Eastern Cooperative Oncology Group (ECOG) Performance Status( PS) 0 or 1.
• Pretreatment tumor biopsy must be a tumor block or 20 unstained slides from biopsy of primary tumor containing at least 20% tumor.
• Willingness to avoid pregnancy or fathering children from screening through 100 days in the US and 190 days in Europe after the last dose of study drug.

Criteri di esclusione: 

• Participation in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) before first dose.
• Previously received systemic therapy for bladder cancer or received prior treatment with checkpoint inhibitor agents (such as anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4).
• Evidence of measurable nodal or metastatic disease.
• Concurrent anticancer therapy.
• Has had major surgery within 4 weeks before enrollment (C1D1).
• Has had known additional malignancy other than muscle-invasive Urothelial Bladder Cancer ( miUBC) that is progressing or requires active treatment, along with some protocol exceptions, or history of other malignancy within 2 years of study entry, with some predefined-protocol exceptions.
• Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg daily doses of prednisone or equivalent) or immunosuppressive drugs within 2 years of Day 1 of study treatment.
• Participants with laboratory values outside of protocol defined ranges.
• Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent).
• Has a known active hepatitis B (defined as HBsAg and total anti-HBc positive results) or hepatitis C (HCV Ab positive result and HCV RNA >LLoD) or HIV,HBV, HCV or hepatitis virus coinfection.
• Participants with HIV+ disease along with protocol defined exceptions that don't have undetectable viral load along with other protocol exceptions.
• Has known carcinomatous meningitis.
• Active infection requiring systemic antibiotics ≤ 14 days from first dose of study drug.
• Participants with known or suspected active COVID-19 infection.
• Use of probiotics within 28 days from first dose of study drug.
• Current use of prohibited medication as per protocol.
• Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention.
• History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 450 milliseconds is excluded.
• History of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) that may affect oral drug absorption.
• Has received a live vaccine within 30days of planned start of study therapy
• Participants with impaired cardiac function or clinically significant cardiac disease
• Prior allogenic tissue/solid organ transplant
• Evidence of interstitial lung disease or active, noninfectious pneumonitis.
• Has known hypersensitivity to any of the study drugs, excipients, including mannitol or another monoclonal antibody which cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
• Any ≥ Grade 2 immune-related toxicity while receiving prior immunotherapy.
• History of serotonin syndrome after receiving 1 or more serotonergic drugs.
• Concomitant use of medications that are known to be substrates of CYP1A2, CYP2C8, or CYP2C19 with narrow therapeutic window are prohibited (see Section 6.6.3).
• Patients who are receiving or required to receive medications that are known to be UGT1A9 inhibitors (see Section 6.6.3).

Trattamento sperimentale: 

Retifanlimab, INCAGN02385, INCAGN02390

Trattamento di controllo: 

NA

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-002244-23

Data di inserimento: 12.07.2023

Promotore

Incyte Corporation

CRO

iQVIA

Principal Investigator ITALIA

IRCCS Ospedale San Raffaele, Milano

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: Milano