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MP68-11 A PHASE 1B STUDY OF PEMBROLIZUMAB (PEMBRO; MK-3475) FOR ADVANCED UROTHELIAL CANCER

2015; Lippincott Williams & Wilkins; Volume: 193; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2015.02.2473

1527-3792

Shilpa Gupta, Peter H. O’Donnell, Elizabeth R. Plimack, Ranaan Berger, Bruce Montgomery, Karl Heath, Marisa Dolled‐Filhart, Kumudu Pathiraja, Christine K. Gause, Jonathan Cheng, Rodolfo F. Perini, Joaquim Bellmunt,

Tissue Engineering and Regenerative Medicine

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2015MP68-11 A PHASE 1B STUDY OF PEMBROLIZUMAB (PEMBRO; MK-3475) FOR ADVANCED UROTHELIAL CANCER Shilpa Gupta, Peter O'Donnell, Elizabeth R. Plimack, Ranaan Berger, Bruce Montgomery, Karl Heath, Marisa Dolled-Filhart, Kumudu Pathiraja, Christine K. Gause, Jonathan Cheng, Rodolfo Perini, and Joaquim Bellmunt Shilpa GuptaShilpa Gupta More articles by this author , Peter O'DonnellPeter O'Donnell More articles by this author , Elizabeth R. PlimackElizabeth R. Plimack More articles by this author , Ranaan BergerRanaan Berger More articles by this author , Bruce MontgomeryBruce Montgomery More articles by this author , Karl HeathKarl Heath More articles by this author , Marisa Dolled-FilhartMarisa Dolled-Filhart More articles by this author , Kumudu PathirajaKumudu Pathiraja More articles by this author , Christine K. GauseChristine K. Gause More articles by this author , Jonathan ChengJonathan Cheng More articles by this author , Rodolfo PeriniRodolfo Perini More articles by this author , and Joaquim BellmuntJoaquim Bellmunt More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2473AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The programmed death-1 (PD-1) pathway can be co-opted by tumor cells to escape immune surveillance. Pembro, a humanized IgG4/kappa isotype monoclonal antibody designed to block the interaction of PD-1 with its ligands PD-L1 and PD-L2, has shown antitumor activity in several advanced solid tumors. The safety, tolerability, and antitumor activity of pembro in patients (pts) with recurrent or metastatic urothelial cancer was assessed in a cohort of KEYNOTE-012 (Clinicaltrials.gov, NCT01848834). METHODS Archival or newly obtained tumor samples from pts with advanced carcinoma of the renal pelvis, ureter, bladder, or urethra were screened for PD-L1 expression using a prototype immunohistochemistry assay. Eligible pts were those with PD-L1 expression in stroma or ≥1% of tumor cells. Pts received pembro 10 mg/kg every 2 wk until complete response, progression, or unacceptable toxicity. Pts deriving benefit could remain on pembro beyond initial progression. Response was assessed every 8 wk per RECIST v1.1 by the investigator and by independent central review (primary efficacy end point). RESULTS A total of 33 pts enrolled (n = 30 with transitional cell histology). Median age was 70 y (range, 44-85), 70% had ECOG PS 1, 52% received 2 prior therapies for advanced disease, and 21% had liver metastases. 22 pts (67%) received ≥3 pembro doses. Median follow-up duration was 11 mo (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 thus 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. Median PFS in pts evaluable for response is 8.8 wk by investigator review and 8.6 wk by central review. In all pts, median OS is 9.3 mo (6-mo OS rate, 58%). CONCLUSIONS Pembro demonstrates promising antitumor activity with acceptable safety and tolerability in pts with advanced urothelial cancer. Ongoing studies are evaluating pembro for the treatment of urothelial cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e861-e862 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Metrics Author Information Shilpa Gupta More articles by this author Peter O'Donnell More articles by this author Elizabeth R. Plimack More articles by this author Ranaan Berger More articles by this author Bruce Montgomery More articles by this author Karl Heath More articles by this author Marisa Dolled-Filhart More articles by this author Kumudu Pathiraja More articles by this author Christine K. Gause More articles by this author Jonathan Cheng More articles by this author Rodolfo Perini More articles by this author Joaquim Bellmunt More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...