Knisely Anne, Hinchcliff Emily M, Gardiner Elisabeth, Rangwala Reshma, Lito Kathryn, Fellman Bryan, Yuan Ying, Sood Anil K, Westin Shannon N, Lu Karen H, Jazaeri Amir A
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Aravive Biologics, Inc, Houston, TX, USA.
iScience. 2024 Apr 23;27(5):109801. doi: 10.1016/j.isci.2024.109801. eCollection 2024 May 17.
Combining an immune checkpoint inhibitor with batiraxcept (AVB-S6-500), an AXL inhibitor that acts via selective binding to growth arrest-specific protein 6 (GAS6), may improve anti-tumor immunity in platinum-resistant ovarian cancer (PROC). This phase 1b trial of durvalumab in combination with escalating doses of batiraxcept enrolled patients with recurrent PROC (NCT04019288). The primary objective was to determine the toxicity profile of the combination. Eleven patients were enrolled on the trial. No dose-limiting toxicities were observed, and no objective responses were noted. Median progression free survival (PFS) was 1.81 months (95% confidence interval (CI) 1.71-2.40), and median overall survival (OS) was 4.53 months (95% CI 2.10-24.74). Batiraxcept effectively reduced serum GAS6 levels at 1-h post-treatment, resulting in trough levels below the limit of detection in all cases but one. In conclusion, the combination of batiraxcept and durvalumab was safe and tolerable but did not demonstrate anti-tumor activity in a heterogenous population of patients with recurrent PROC.
将免疫检查点抑制剂与batiraxcept（AVB-S6-500）联合使用，batiraxcept是一种AXL抑制剂，通过选择性结合生长停滞特异性蛋白6（GAS6）发挥作用，可能会提高铂耐药卵巢癌（PROC）的抗肿瘤免疫力。这项度伐利尤单抗联合递增剂量batiraxcept的1b期试验纳入了复发性PROC患者（NCT04019288）。主要目的是确定联合用药的毒性特征。11名患者参加了该试验。未观察到剂量限制性毒性，也未观察到客观缓解。中位无进展生存期（PFS）为1.81个月（95%置信区间（CI）1.71-2.40），中位总生存期（OS）为4.53个月（95%CI 2.10-24.74）。Batiraxcept在治疗后1小时有效降低血清GAS6水平，除1例患者外，所有患者的谷值水平均低于检测下限。总之，batiraxcept和度伐利尤单抗联合用药安全且耐受性良好，但在复发性PROC患者的异质性群体中未显示出抗肿瘤活性。
