Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings
Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings
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DOI：
10.2217/imt-2020-0256
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发表时间：
2020-11-11
期刊：
影响因子：
2.8
通讯作者：
Bargou, Ralf C.
中科院分区：
文献类型：
--
作者：
Hummel, Horst-Dieter;Kufer, Peter;Bargou, Ralf C.
目的：我们报告了pasotuizumab的首次人体研究结果，pasotuizumab是一种PSMA双特异性t细胞接触器（BiTE (R)）免疫疗法，可介导晚期去势抵抗性前列腺癌患者肿瘤细胞的t细胞杀伤。患者和方法：我们评估了每日一次皮下（SC）帕索妥珠单抗。所有SC患者均产生抗药物抗体；因此，评估了持续静脉输液（cIV）。结果：共有47例患者接受帕索妥珠单抗治疗（SC: n = 31, 0.5 ~ 172 μ g/d; cIV: n = 16, 5 ~ 80 μ g/d）。SC最大耐受剂量为172.0 μ g/d。赞助商的改变提前终止了《文明》群组；最大耐受剂量未确定。出现了PSA应答（>50% PSA下降：SC， n = 9; cIV, n = 3），包括2名长期应答者。结论：数据支持pasotuxizumab治疗晚期去势抵抗性前列腺癌的安全性，并代表了BiTE单药治疗实体瘤疗效的证据。临床试验注册：NCT01723475 （ClinicalTrials.gov）
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)