Resumen

The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.
Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Have adequate organ function.

Criterios de exclusión

Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
Has ≥N2 disease or metastatic disease (M1) as identified by imaging
Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
Has a known psychiatric or substance abuse disorder
Has had an allogenic tissue/solid organ transplant
Has ongoing sensory or motor neuropathy Grade 2 or higher
Has active keratitis (superficial punctate keratitis) or corneal ulcerations
Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms

Intervenciones

biological

Pembrolizumab

200 mg of Pembrolizumab IV infusion, on Day 1 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 Q3W for 13 cycles in postoperative phase (up to approximately 9 months). The total duration of treatment is up to approximately 1 year.

biological

Enfortumab vedotin (EV)

1.25 mg/kg of EV IV infusion, on Day 1 and Day 8 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 and Day 8 Q3W for 5 cycles (each cycle length = 21 days) in postoperative phase (up to approximately 4 months). The total duration of treatment is up to approximately 7 months.

procedure

RC + PLND

Curative intent RC + PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC + PLND to be done approximately at 15 weeks from randomization).

drug

Gemcitabine

1000 mg/m\^2 of Gemcitabine IV infusion, Day 1 and Day 8 Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

drug

Cisplatin

70 mg/m\^2 of Cisplatin IV infusion, Day 1, Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

Ubicaciones

Hospital Británico de Buenos Aires-Oncology ( Site 1551)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Hospital Italiano de Buenos Aires ( Site 1554)

ABB, Buenos Aires F.D., Argentina

Asociación de Beneficencia Hospital Sirio Libanés ( Site 1553)

Buenos Aires, Buenos Aires F.D., Argentina

Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 1558)