KEYNOTE-052: Phase 2 study of pembrolizumab (MK-3475) as first-line therapy for patients (pts) with unresectable or metastatic urothelial cancer ineligible for cisplatin-based therapy.

Abstract

TPS4572 Background: Standard first-line therapy for advanced urothelial cancer is cisplatin-based chemotherapy. Pts who are ineligible for cisplatin therapy, mainly due to renal dysfunction and/or poor performance status, have limited treatment options. The programmed death receptor 1 (PD-1) pathway is used by tumors to suppress immune control. Pembrolizumab is a highly selective, IgG4 anti-PD-1 humanized monoclonal antibody designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2. In the phase 1 KEYNOTE-012 trial, pembrolizumab 10 mg/kg once every 2 weeks (Q2W) demonstrated an ORR of 24% (RECIST v1.1, central review) in 33 pts with PD-L1–positive advanced urothelial cancer, 76% of whom received ≥ 1 prior therapy. Methods: KEYNOTE-052 (ClinicalTrials.gov, NCT02335424) is an international, open-label, phase 2 trial of pembrolizumab 200 mg Q3W as first-line therapy for adults with unresectable or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra who are ineligible to receive cisplatin. Pts are considered cisplatin ineligible if they have ≥ 1 of the following: ECOG PS 2, creatinine clearance (calculated or measured) < 60 but ≥ 30 mL/min, grade ≥ 2 (CTCAE v4) audiometric hearing loss or peripheral neuropathy, or NYHA class III heart failure. All pts must provide a recently obtained biopsy sample for PD-L1 evaluation at a central laboratory. Pembrolizumab will be given for up to 24 mo or until disease progression, unacceptable toxicity, or investigator decision; treatment may be discontinued following complete response. Select pts may continue pembrolizumab beyond initial evidence of radiographic progression. Response will be evaluated per RECIST v1.1 by independent central review at 9 wk and every 6 wk thereafter. Survival follow-up will occur every 3 mo. Primary end point is ORR in pts with PD-L1–dependent tumors. Secondary end points include ORR in all pts, PFS, OS, duration of response, and the association between PD-L1 positivity and ORR. Up to 350 pts will be enrolled. KEYNOTE-052 is currently enrolling pts. Clinical trial information: NCT02335424.