PD32-05 PHASE I CLINICAL STUDY ON THE COMBINATION THERAPY OF CHP-NY-ESO-1 CANCER VACCINE AND MIS416 FOR THE TREATMENT OF PATIENTS WITH NY-ESO-1 EXPRESSING REFRACTORY UROTHELIAL CANCER OR CASTRATION-RESISTANT PROSTATE CANCER

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You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III1 Apr 2016PD32-05 PHASE I CLINICAL STUDY ON THE COMBINATION THERAPY OF CHP-NY-ESO-1 CANCER VACCINE AND MIS416 FOR THE TREATMENT OF PATIENTS WITH NY-ESO-1 EXPRESSING REFRACTORY UROTHELIAL CANCER OR CASTRATION-RESISTANT PROSTATE CANCER Takeshi Sasaki, Mikiya Ishihara, Hideki Kanda, Yasuhide Hori, Norihito Soga, Naozumi Harada, Yoshihiro Miyahara, Shinichi Kageyama, Hiroshi Shiku, and Yoshiki Sugimura Takeshi SasakiTakeshi Sasaki More articles by this author , Mikiya IshiharaMikiya Ishihara More articles by this author , Hideki KandaHideki Kanda More articles by this author , Yasuhide HoriYasuhide Hori More articles by this author , Norihito SogaNorihito Soga More articles by this author , Naozumi HaradaNaozumi Harada More articles by this author , Yoshihiro MiyaharaYoshihiro Miyahara More articles by this author , Shinichi KageyamaShinichi Kageyama More articles by this author , Hiroshi ShikuHiroshi Shiku More articles by this author , and Yoshiki SugimuraYoshiki Sugimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.681AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES NY-ESO-1 antigen is a cancer-testis antigen that is exclusively expressed in several types of cancer, aside from expression in the normal testis and placenta. This antigen is considered an ideal target for cancer immunotherapy. Cholesteryl pullulan (CHP) is a novel antigen delivery system. Complexes of CHP and NY-ESO-1 antigen (CHP-NY-ESO-1) present multiple epitope peptides to both the MHC class I and class II pathways. MIS416 is a non-toxic microparticle adjuvant that activates immune responses via NOD-2 and TLR9 pathways. Vaccination studies in mice had demonstrated that CHP-NY-ESO-1 with MIS416 enhanced anti-tumor efficacy. This study evaluated the safety, tolerability, and clinical efficacy of CHP-NY-ESO-1 with adjuvant MIS416 in NY-ESO-1-expressing patients (pts) with refractory urothelial cancer (UC) or castration-resistant prostate cancer (CRPC) (Clinical trial registration number, UMIN000005246). METHODS Archival or newly obtained tumor samples from pts were screened for NY-ESO-1 expression using immunohistochemistry and RT-PCR. Eligible pts were those with NY-ESO-1 expression in ≥1% of tumor cells and/or ≥NY-ESO-1 1 copy/GADPH 104 copy. Pts received CHP-NY-ESO-1/MIS416 100 μg/200 μg, 200 μg/200 μg, 200 μg/400 μg, or 200 μg/600 μg every 2 wk 6 doses followed by every 4 wks vaccination until disease progression or unacceptable toxicity was observed. Response was assessed at 12 wks by CT and bone scan per RECIST v1.1 and serum PSA levels. The primary endpoints were safety and tolerability, and the secondary endpoints were clinical efficacy and quality of life. RESULTS A total of 16 pts were enrolled (4 pts with UC and 12 pts with CRPC). Median age was 74 y (range, 48-84). All pts had prior therapies (chemotherapy, radiation, and/or surgery). Five were repeatedly vaccinated with 100 µg (median 4.5 [1-7] doses) and 10 pts with 200 μg (6 [3-37] doses) of CHP-NY-ESO-1. Ten pts (63%) received ≥6 doses. One pt remains on therapy. G1-2 drug-related adverse event (AE) was observed in all pts, most commonly injection site reaction (n = 16), malaise (n = 3), sinus tachycardia (n = 3), and hyperkalemia (n = 3). Grade 3 drug-related AEs were observed in 5 pts (31%), hypertension (n = 3) and anorexia (n = 1). No G4 drug-related AEs were observed. All pts with refractory UC had PD <6 doses. In CRPC pts, 4 pts (48%) had SD, 7 pts (58%) had PD, and one pt had N/A. No significant difference was seen in QLQ-C30 symptom score during treatment. CONCLUSIONS CHP-NY-ESO-1 with adjuvant MIS416 demonstrates acceptable safety and tolerability in refractory UC and CRPC pts with promising anti-tumor efficacy in CRPC pts. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e762 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Takeshi Sasaki More articles by this author Mikiya Ishihara More articles by this author Hideki Kanda More articles by this author Yasuhide Hori More articles by this author Norihito Soga More articles by this author Naozumi Harada More articles by this author Yoshihiro Miyahara More articles by this author Shinichi Kageyama More articles by this author Hiroshi Shiku More articles by this author Yoshiki Sugimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...