Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: Results of a phase IB study.

Abstract

296 Background: Pembro, an anti-PD-1 monoclonal antibody, has shown antitumor activity in several advanced solid tumors. The safety, tolerability, and antitumor activity of pembro in pts with recurrent or metastatic urothelial cancer was assessed in a cohort of KEYNOTE-012 (Clinicaltrials.gov: NCT01848834). Methods: PD-L1 expression was assessed in archival or newly obtained tumor samples from pts with advanced carcinoma of the renal pelvis, ureter, bladder, or urethra using a prototype immunohistochemistry assay. Only pts with PD-L1 expression in stroma or ≥1% of tumor cells were eligible. Pts received pembro 10 mg/kg every 2 wks until complete response, progression, or unacceptable toxicity. Pts deriving benefit could remain on pembro beyond initial progression. Response was assessed every 8 wks per RECIST v1.1 by the investigator and by independent central review (primary efficacy end point). Results: 33 pts enrolled (n=30 with transitional cell histology; median age, 70 y [range 44-85]; ECOG PS 1, 70%; 2 prior therapies for advanced disease, 52%; liver metastases, 21%). 22 pts (67%) received ≥3 pembro doses. Median follow-up duration was 11 mos (range 10-13), and 7 pts (21%) remain on therapy. At least 1 drug-related AE was reported by 61% of pts, most commonly fatigue (n=6), peripheral edema (n=4), and nausea (n=3). Grade 3-4 drug-related AEs were reported for 4 pts (12%), with only rash seen in >1 pt (n=2). 29 pts received ≥1 dose of pembro and had a baseline scan with measurable disease and were evaluable for response. ORR was 24% (95% CI, 10%-44%) by investigator review, with 7 partial responses. ORR by central review was also 24% (95% CI, 10%-44%), with 3 (10%) complete and 4 (14%) partial responses. Response duration is 16-40+ wk (median not reached) by both investigator and central review. ORR in key subgroups, including visceral vs. nodal metastasis, will be presented. In pts evaluable for response, median PFS is 8.8 wks by investigator review and 8.6 wks by central review. In all pts, median OS is 9.3 mos (6-mo OS rate, 58%). Conclusions: Pembro shows acceptable safety and tolerability and provides promising antitumor activity in pts with advanced urothelial cancer. Evaluation of pembro for the treatment of urothelial cancer is ongoing. Clinical trial information: NCT01848834.