Dados do Trabalho

Título

BACILLUS CALMETTE-GUERIN WITH PEMBROLIZUMAB IN PATIENTS WITH BACILLUS CALMETTE-GUERIN–NAIVE HIGH-RISK NON–MUSCLE-INVASIVE BLADDER CANCER: COHORT B OF THE PHASE 3 KEYNOTE-676 STUDY

Introdução e Objetivo

Intravesical instillation of bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non–muscle-invasive bladder cancer (NMIBC). Pembrolizumab showed antitumor activity in the phase 2 KEYNOTE-057 study with manageable safety in patients with BCG-unresponsive high-risk NMIBC with carcinoma in situ (CIS; cohort A) and in patients with papillary tumors only (cohort B). Cohort B of the comparator-controlled, open-label, phase 3 KEYNOTE-676 study (NCT03711032) will evaluate pembrolizumab + BCG versus BCG alone in BCG-naive patients.    

Método

Adult patients with high-risk NMIBC (T1, high-grade Ta, and/or CIS) confirmed by blinded independent central review who underwent cystoscopy/TURBT ≤12 week before randomization, have ECOG PS 0-2, and had not received BCG for ≤2 years will be eligible to enroll. Patients will be randomly assigned 1:1:1 to receive pembrolizumab 400 mg intravenously every 6 weeks + BCG reduced maintenance (≤6 months), pembrolizumab 400 mg intravenously every 6 weeks + BCG full maintenance (≤18 months), or BCG monotherapy (BCG full maintenance). Treatment will continue until central pathology–confirmed high-grade Ta or any CIS at 24 weeks or thereafter, T1 or higher at any time point, disease progression to muscle-invasive bladder cancer or metastatic bladder cancer, unacceptable toxicity, or withdrawal. Patients will be stratified by PD-L1 expression (combined positive score [CPS] ≥10 or CPS <10) and NMIBC stage (CIS or non-CIS), determined by central laboratory. Primary end point is comparison of event-free survival between treatment arms (pembrolizumab + BCG [reduced maintenance] vs BCG alone and pembrolizumab + BCG [full maintenance] vs BCG alone). Secondary end points are comparison of complete response rate by blinded independent central review, recurrence free survival, time to cystectomy, disease-specific survival, health-related quality of life, and overall survival between treatment arms; and evaluation of 24-month event-free survival rate; duration of response and 12-month duration of response rate for patients who achieve complete response (CIS only); and safety within treatment arms.

Resultados

Approximately 975 patients will be enrolled in KEYNOTE-676 cohort B. Recruitment is ongoing in Asia, Europe, North America, and South America.

Conclusão

Results will elucidate the role of pembrolizumab + BCG combination therapy in BCG treatment-naive patients with high-risk NMIBC.