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

Aim: We report results of a first-in-human study of pasotuxizumab, a PSMA bispecific T-cell engager (BiTE®) 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 μg/d; cIV: n = 16, 5-80 μg/d). The SC maximum tolerated dose was 172.0 μg/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).

Immunotherapy. 2020 Nov 10 [Epub ahead of print]

Horst-Dieter Hummel, Peter Kufer, Carsten Grüllich, Ruth Seggewiss-Bernhardt, Barbara Deschler-Baier, Manik Chatterjee, Maria-Elisabeth Goebeler, Kurt Miller, Maria de Santis, Wolfgang Loidl, Christian Dittrich, Andreas Buck, Constantin Lapa, Annette Thurner, Sabine Wittemer-Rump, Gökben Koca, Oliver Boix, Wolf-Dietrich Döcke, Ricarda Finnern, Helena Kusi, Antoinette Ajavon-Hartmann, Sabine Stienen, Cyrus Michael Sayehli, Bülent Polat, Ralf C Bargou

Translational Oncology/Early Clinical Trial Unit (ECTU), Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080 Würzburg, Germany., Research and Development, Amgen Research Munich GmbH, Staffelseestr. 2, 81477, Munich, Germany., Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Medical Center, Heidelberg, Germany; & Department of Oncology & Hematology, University Hospital Dresden, Haus 27, Fetscherstr. 74, 01307 Dresden, Germany., Translational Oncology, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Josef-Schneider-Str. 6, 97080 Würzburg, Germany., Translational Oncology/Early Clinical Trial Unit (ECTU), Medizinische Klinik II, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080 Würzburg, Germany., Department of Urology, Charité Universitätsmedizin Berlin, Charitéplatz. 1, 10117, Berlin, Germany., Department of Urology, Ordensklinikum Linz GmbH Elisabethinen, Fadingerstr. 1, 4020, Linz, Austria., Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna) & Center for Oncology & Hematology, Kaiser Franz Josef-Spital, Bernardgasse 24/2, 1070, Vienna, Austria., Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacherstr. 6, D-97080, Würzburg, Germany., Department of Diagnostic & Interventional Radiology, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany., Bayer AG, SBU Oncology, Pharmaceuticals, 13353, Berlin, Germany., Department of Radiation Oncology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.