Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Hematology and Medical Oncology, University Cancer & Blood Center, Athens, Georgia.
J Thorac Oncol. 2021 Sep;16(9):1559-1569. doi: 10.1016/j.jtho.2021.02.022. Epub 2021 Feb 27.
This open-label, phase 1-2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC).
Patients with histologically or cytologically confirmed, previously treated (two or more lines of therapy) ES SCLC were enrolled into two cohorts. Cohort 1 received 0.3 mg/kg Rova-T (once every 6 wk for two cycles) plus 360 mg nivolumab (two 3-wk cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as cohort 1 plus 1 mg/kg nivolumab (four 3-wk cycles) and 1 mg/kg ipilimumab (beginning week 4). Both cohorts received 480 mg nivolumab every 4 weeks starting at week 10. Key objectives were to evaluate safety and tolerability and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1). The response-related results are based on centrally read data.
A total of 42 patients received therapy: cohort 1, n = 30; cohort 2, n = 12. Overall, 43% received two or more previous lines of therapy. All patients experienced one or more treatment-emergent adverse event (TEAE); 41 patients reported AEs considered related to the study drug by the investigator. The most frequent TEAE was pleural effusion (n = 20, 48%); most common grade greater than or equal to 3 was anemia (n = 9, 21%). Three grade 5 TEAEs considered related to the study drug were reported (cohort 1): pneumonitis (n = 2), acute kidney injury (n = 1). The objective response rate was 30% (12 of 40): cohort 1, 27.6% (8 of 29); cohort 2, 36.4% (4 of 11); all partial responses.
Despite encouraging antitumor activity in previously treated ES SCLC, combination therapy with Rova-T and nivolumab plus or minus ipilimumab was not well tolerated at the dose levels and administration schedules evaluated.
这是一项开放标签、1-2 期研究，评估了靶向 DLL3 的抗体药物偶联物 rovalpituzumab tesirine（Rova-T）联合免疫检查点抑制剂纳武利尤单抗加或不加伊匹单抗治疗既往治疗广泛期小细胞肺癌（ES SCLC）的安全性和疗效。
组织学或细胞学确认的既往治疗（两种或两种以上治疗线）ES SCLC 患者入组两个队列。队列 1 患者接受 0.3 mg/kg Rova-T（每 6 周一次，共两个周期）加 360 mg 纳武利尤单抗（第 4 周开始的两个 3 周周期）。队列 2 患者接受与队列 1 相同剂量的 Rova-T，加 1 mg/kg 纳武利尤单抗（第 4 周开始的四个 3 周周期）和 1 mg/kg 伊匹单抗。两组患者均在第 10 周开始每 4 周接受 480 mg 纳武利尤单抗。主要终点是评估安全性和耐受性以及疗效（根据实体瘤反应评估标准 1.1 版）。反应相关结果基于中心评估数据。
共有 42 名患者接受治疗：队列 1，n=30；队列 2，n=12。所有患者均接受过两种或两种以上的既往治疗线。所有患者均发生一次或多次治疗相关不良事件（TEAE）；41 名患者报告了研究者认为与研究药物相关的 AE。最常见的 TEAE 是胸腔积液（n=20，48%）；最常见的 3 级以上不良事件是贫血（n=9，21%）。报告了 3 例研究者认为与研究药物相关的 5 级 TEAEs（队列 1）：肺炎（n=2），急性肾损伤（n=1）。客观缓解率为 30%（40 例中的 12 例）：队列 1，27.6%（29 例中的 8 例）；队列 2，36.4%（11 例中的 4 例）；均为部分缓解。
尽管在既往治疗的 ES SCLC 中观察到有抗肿瘤活性，但在评估的剂量水平和给药方案下，Rova-T 联合纳武利尤单抗加或不加伊匹单抗的联合治疗不耐受。
