Horst-Dieter Hummel1, Peter Kufer2, Carsten Grüllich3, Ruth Seggewiss-Bernhardt1,4, Barbara Deschler-Baier5, Manik Chatterjee1, Maria-Elisabeth Goebeler6, Kurt Miller7, Maria de Santis7,8, Wolfgang Loidl9, Christian Dittrich10, Andreas Buck11, Constantin Lapa11,12, Annette Thurner13, Sabine Wittemer-Rump14, Gökben Koca14, Oliver Boix14, Wolf-Dietrich Döcke14, Ricarda Finnern14, Helena Kusi14, Antoinette Ajavon-Hartmann14, Sabine Stienen2, Cyrus Michael Sayehli6, Bülent Polat15, Ralf C Bargou5. 1. Translational Oncology/Early Clinical Trial Unit (ECTU), Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080 Würzburg, Germany. 2. Research and Development, Amgen Research Munich GmbH, Staffelseestr. 2, 81477, Munich, Germany. 3. 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. 4. Medizinische Klinik V, Sozialstiftung Bamberg, Buger Str. 80, 96049, Bamberg, Germany. 5. Translational Oncology, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Josef-Schneider-Str. 6, 97080 Würzburg, Germany. 6. Translational Oncology/Early Clinical Trial Unit (ECTU), Medizinische Klinik II, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080 Würzburg, Germany. 7. Department of Urology, Charité Universitätsmedizin Berlin, Charitéplatz. 1, 10117, Berlin, Germany. 8. Department of Urology, Medical University Vienna, Währinger Gürtel 18-20; 1090 Vienna, Austria. 9. Department of Urology, Ordensklinikum Linz GmbH Elisabethinen, Fadingerstr. 1, 4020, Linz, Austria. 10. 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. 11. Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacherstr. 6, D-97080, Würzburg, Germany. 12. Nuclear Medicine, Medical Faculty, University of Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany. 13. Department of Diagnostic & Interventional Radiology, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany. 14. Bayer AG, SBU Oncology, Pharmaceuticals, 13353, Berlin, Germany. 15. Department of Radiation Oncology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
Abstract
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).
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).
Entities:
Keywords:
AMG 212; BAY 2010112; PSMA; bispecific T-cell engager (BiTE®) immune therapy; pasotuxizumab; prostate cancer
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