Dados do Trabalho

Título

BACILLUS CALMETTE-GUERIN WITH OR WITHOUT PEMBROLIZUMAB FOR HIGH-RISK NON–MUSCLE-INVASIVE BLADDER CANCER THAT PERSISTS/RECURS AFTER BACILLUS CALMETTE-GUERIN INDUCTION: COHORT A OF THE PHASE 3 KEYNOTE-676 STUDY

Introdução e Objetivo

Standard of care for patients with high-risk (HR) non–muscle invasive bladder cancer (NMIBC) is intravesical instillation of bacillus Calmette-Guérin (BCG), but patients risk disease recurrence or progression to muscle-invasive bladder cancer (MIBC). Pembrolizumab monotherapy showed antitumor activity in the phase 2 KEYNOTE-057 study for patients with HR BCG­–unresponsive NMIBC who were ineligible for or had elected not to undergo radical cystectomy. Cohort A of the randomized, phase 3 KEYNOTE-676 trial (NCT03711032) will evaluate pembrolizumab + BCG in patients with persistent/recurrent HR NMIBC after first BCG induction.

Método

Eligible adults have histologically confirmed persistent/recurrent HR NMIBC (T1, high-grade Ta, and/or CIS) after adequate first BCG induction, no concurrent extravesical disease or history of extravesical disease that recurred ≤2 years, ECOG PS score of 0-2, and have undergone cystoscopy/TURBT ≤12 weeks before randomization. Patients will be randomly assigned 1:1 to BCG + pembrolizumab 200 mg IV every 3 weeks or BCG alone. BCG (50 mg) will be administered by intravesical instillation as induction therapy (once weekly for 6 weeks) and then as maintenance therapy first at 12-week intervals for the first 2 cycles and then at 6-month intervals. Treatment will be randomly stratified by PD-L1 combined positive score (≥10/˂10), histology (presence/absence of CIS), and NMIBC disease history (persistence/recurrence 0 to ≤6 months, recurrence ˃6 to ≤12 months, or recurrence ˃12 to ≤24 months). Treatment will continue for ≤2 years (pembrolizumab) or 3 years (BCG), or until confirmed persistent/recurrent HR NMIBC or disease progression to MIBC or metastatic bladder cancer, unacceptable toxicity, or withdrawal. Primary end point is complete response rate in patients with CIS ± papillary tumors. Key secondary end point is event-free survival; other secondary end points are duration of response (complete responders with CIS only), recurrence-free survival, time to cystectomy, overall survival, disease-specific survival, safety and tolerability, and patient-reported outcomes.

Resultados

Cohort A of KEYNOTE-676 will enroll ~430 patients; recruitment is ongoing in Asia, Australia, Europe, and North America.

Conclusão

Results of this study will elucidate the role of pembrolizumab + BCG combination therapy after BCG induction in patients with persistent/recurrent HR NMIBC.