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

被引：95

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

来源：

IMMUNOTHERAPY | 2021年 / 13卷 / 02期

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

页码：125 / 141

页数：18

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