塔拉拉他单抗治疗神经内分泌前列腺癌患者的安全性和有效性：1b期DeLLpro-300研究结果

Safety and Efficacy of Tarlatamab in patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study.

作者信息

Aggarwal Rahul, Rottey Sylvie, Bernard-Tessier Alice, Mellado Begoña, Kosaka Takeo, Stadler Walter M, Horvath Lisa, Greil Richard, O'Neil Bert, Siddiqui Bilal A, Bauernhofer Thomas, Bilen Mehmet A, Eskens Ferry, Sandhu Shahneen, Shaw Crystal, Ju Chia Hsin, Decato Benjamin E, Yu Brian, Aparicio Ana

机构信息

University of California, San Francisco, San Francisco, CA, United States.

Ghent University Hospital - 4B11, Ghent, Belgium.

出版信息

Clin Cancer Res. 2025 Jul 21. doi: 10.1158/1078-0432.CCR-25-1211.

DOI:10.1158/1078-0432.CCR-25-1211

PMID:40689871

Abstract

PURPOSE

Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer with poor prognosis and limited treatment options. As NEPC aberrantly expresses delta-like ligand 3 (DLL3), the activity of tarlatamab, a bispecific T-cell engager (BiTE®) that directs cytotoxic T cells to DLL3‑positive (DLL3+) cells, was evaluated in the DeLLpro-300 study (NCT04702737).

PATIENTS AND METHODS

This was a phase 1b, open-label study evaluating tarlatamab monotherapy in patients with metastatic de novo or treatment-emergent NEPC defined by histologic, genomic, or immunohistochemistry (IHC) criteria. Tarlatamab was administered intravenously every 2 weeks at a dose of 100 mg with a 1-mg step dose. The primary objective was safety, and a secondary objective was objective response rate (ORR) per RECIST v.1.1; DLL3 expression was retrospectively assessed by IHC.

RESULTS

Forty patients were enrolled (DLL3+ tumors, n=18; DLL3- tumors, n=14; DLL3 unknown tumors, n=8). The most common treatment-related adverse events were cytokine release syndrome (CRS; 82.5%), dysgeusia (42.5%), and decreased appetite (40.0%). CRS was predominantly low grade (grade 1/2/3/4+, 62.5%/15%/5%/0%), occurred exclusively in cycle 1, and was transient in duration (median duration, 3 days). ORR was 10.5% (95% CI, 2.9-24.8); the median duration of response was 7.3 months in the overall cohort. Patients with DLL3+ tumors (vs patients with DLL3-/DLL3 unknown tumors) acheived a higher ORR (22.2% [95% CI, 6.4-47.6] vs 0% [95% CI, 0-15.4]) and radiographic progression-free survival rate at 6 months (27.7% [95% CI, 8.7-50.9] vs 0%).

CONCLUSIONS

The DeLLpro-300 study provides preliminary evidence for the safety and antitumor activity of tarlatamab in DLL3+ NEPC.

摘要

目的

神经内分泌前列腺癌（NEPC）是一种侵袭性前列腺癌，预后较差且治疗选择有限。由于NEPC异常表达δ样配体3（DLL3），在DeLLpro - 300研究（NCT04702737）中评估了tarlatamab（一种双特异性T细胞衔接器（BiTE®），可将细胞毒性T细胞导向DLL3阳性（DLL3 +）细胞）的活性。

患者与方法

这是一项1b期开放标签研究，评估tarlatamab单药治疗转移性初发或治疗中出现的NEPC患者，这些患者由组织学、基因组学或免疫组织化学（IHC）标准定义。Tarlatamab每2周静脉注射一次，剂量为100mg，有1mg的阶梯剂量。主要目标是安全性，次要目标是根据RECIST v.1.1标准的客观缓解率（ORR）；通过IHC回顾性评估DLL3表达。

结果

共入组40例患者（DLL3 +肿瘤患者18例；DLL3 -肿瘤患者14例；DLL3情况未知肿瘤患者8例）。最常见的治疗相关不良事件为细胞因子释放综合征（CRS；82.5%）、味觉障碍（42.5%）和食欲下降（40.0%）。CRS主要为低级别（1/2/3/4 +级，分别为62.5%/15%/5%/0%），仅在第1周期出现，持续时间短暂（中位持续时间为3天）。ORR为10.5%（95%CI，2.9 - 24.8）；总体队列中缓解的中位持续时间为7.3个月。DLL3 +肿瘤患者（与DLL3 - /DLL3情况未知肿瘤患者相比）的ORR更高（22.2% [95%CI，6.4 - 47.6] 对0% [95%CI，0 - 15.4]），6个月时的影像学无进展生存率也更高（27.7% [95%CI，8.7 - 50.9] 对0%）。