Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings

被引:87
作者
Hummel, Horst-Dieter [1 ]
Kufer, Peter [2 ]
Gruellich, Carsten [3 ,4 ]
Seggewiss-Bernhardt, Ruth [1 ,5 ]
Deschler-Baier, Barbara [6 ]
Chatterjee, Manik [1 ]
Goebeler, Maria-Elisabeth [7 ]
Miller, Kurt [8 ]
de Santis, Maria [8 ,9 ]
Loidl, Wolfgang [10 ]
Dittrich, Christian [11 ,12 ]
Buck, Andreas [13 ]
Lapa, Constantin [13 ,14 ]
Thurner, Annette [15 ]
Wittemer-Rump, Sabine [16 ]
Koca, Gokben [16 ]
Boix, Oliver [16 ]
Doecke, Wolf-Dietrich [16 ]
Finnern, Ricarda [16 ]
Kusi, Helena [16 ]
Ajavon-Hartmann, Antoinette [16 ]
Stienen, Sabine [2 ]
Sayehli, Cyrus Michael [17 ]
Polat, Buelent [18 ]
Bargou, Ralf C. [6 ]
机构
[1] Univ Hosp Wurzburg, Comprehens Canc Ctr Mainfranken, Translat Oncol Early Clin Trial Unit ECTU, Oberdurrbacherstr 6, D-97080 Wurzburg, Germany
[2] Amgen Res Munich GmbH, Res & Dev, Staffelseestr 2, D-81477 Munich, Germany
[3] Heidelberg Univ, Med Ctr, Natl Ctr Tumor Dis, Dept Med Oncol, Heidelberg, Germany
[4] Univ Hosp Dresden, Dept Hematol & Oncol, Haus 27,Fetscherstr 74, D-01307 Dresden, Germany
[5] Sozialstiftung Bamberg, Med Klin 5, Buger Str 80, D-96049 Bamberg, Germany
[6] Univ Hosp Wurzburg, Comprehens Canc Ctr Mainfranken, Translat Oncol, Josef Schneider Str 6, D-97080 Wurzburg, Germany
[7] Univ Hosp Wurzburg, Med Klin 2, Translat Oncol Early Clin Trial Unit ECTU, Oberdurrbacherstr. 6, D-97080 Wurzburg, Germany
[8] Charite Univ Med Berlin, Dept Urol, Charitepl 1, D-10117 Berlin, Germany
[9] Med Univ Vienna, Dept Urol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria
[10] Ordensklinikum Linz GmbH Elisabethinen, Dept Urol, Fadingerstr 1, A-4020 Linz, Austria
[11] Kaiser Franz Josef Spital, Inst Translat Res Vienna ACRI TR VIEnna, Appl Canc Res, Bernardgasse 24-2, A-1070 Vienna, Austria
[12] Kaiser Franz Josef Spital, Ctr Oncol & Hematol, Bernardgasse 24-2, A-1070 Vienna, Austria
[13] Univ Hosp Wurzburg, Dept Nucl Med, Oberdurrbacherstr 6, D-97080 Wurzburg, Germany
[14] Univ Augsburg, Med Fac, Nucl Med, Stenglinstr 2, D-86156 Augsburg, Germany
[15] Univ Hosp Wurzburg, Dept Diagnost & Intervent Radiol, Oberdurrbacherstr 6, D-97080 Wurzburg, Germany
[16] Bayer AG, SBU Oncol, Pharmaceut, D-13353 Berlin, Germany
[17] Univ Hosp Wurzburg, Med Klin 2, Translat Oncol Early Clin Trial Unit ECTU, Oberdurrbacherstr 6, D-97080 Wurzburg, Germany
[18] Univ Hosp Wurzburg, Dept Radiat Oncol, Josef Schneider Str 11, D-97080 Wurzburg, Germany
关键词
AMG; 212; BAY; 2010112; bispecific T-cell engager (BiTE (R)) immune therapy; pasotuxizumab; PSMA; prostate cancer; MEMBRANE ANTIGEN; T-CELLS; NIVOLUMAB; CHEMOTHERAPY; ANTIBODY; PEMBROLIZUMAB; IPILIMUMAB; REGRESSION; CARCINOMA;
D O I
10.2217/imt-2020-0256
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Aim: We report results of a first-in-human study of pasotuxizumab, a PSMA bispecific T-cell engager (BiTE (R)) immune therapy mediating T-cell killing of tumor cells in patients with advanced castration-resistant prostate cancer. Patients & methods: We assessed once-daily subcutaneous (SC) pasotuxizumab. All SC patients developed antidrug antibodies; therefore, continuous intravenous (cIV) infusion was assessed. Results: A total of 47 patients received pasotuxizumab (SC: n = 31, 0.5-172 mu g/d; cIV: n = 16, 5-80 mu g/d). The SC maximum tolerated dose was 172.0 mu g/d. A sponsor change stopped the cIV cohort early; maximum tolerated dose was not determined. PSA responders occurred (>50% PSA decline: SC, n = 9; cIV, n = 3), including two long-term responders. Conclusion: Data support pasotuxizumab safety in advanced castration-resistant prostate cancer and represent evidence of BiTE monotherapy efficacy in solid tumors. Clinical trial registration:NCT01723475 (ClinicalTrials.gov)
引用
收藏
页码:125 / 141
页数:18
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