Emory University, Winship Cancer Institute, Atlanta, Georgia.
Oncology Institute of Hope and Innovation, Los Angeles, California.
Cancer. 2022 Jan 1;128(1):65-74. doi: 10.1002/cncr.33885. Epub 2021 Sep 3.
Poly(ADP-ribose) polymerase (PARP) inhibitors may synergize with programmed cell death receptor-1 (PD-1) inhibitors to enhance adaptive and innate antitumor immune responses. In the phase 2 JASPER study (NCT04475939), the PARP inhibitor niraparib was evaluated in combination with the PD-1 inhibitor pembrolizumab in patients with metastatic and/or locally advanced non-small cell lung cancer (NSCLC).
Patients whose tumors had programmed cell death ligand 1 (PD-L1) tumor proportion scores (TPS) ≥50% (cohort 1) or 1%-49% (cohort 2) received first-line niraparib (200 mg once daily) plus pembrolizumab (200 mg every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics.
Thirty-eight patients were enrolled in cohorts 1 and 2. In cohort 1, ORR (95% confidence interval [CI]) was 56.3% (9 of 16 patients; 29.9%-80.2%); 2 of 16 patients had complete responses and 7 of 16 had partial responses (PRs). In cohort 2, ORR was 20.0% (5.7%-43.7%) with 4 of 20 PRs. In cohorts 1 and 2, the median DoR was 19.7 months (95% CI, 4.2 months to not estimable [NE]) and 9.4 months (95% CI, 4.2 months to NE), the median PFS was 8.4 months (95% CI, 3.9-22.1 months) and 4.2 months (95% CI, 2.0-6.2 months), and the median OS was NE (95% CI, 6.0 months to NE) and 7.7 months (95% CI, 4.0-12.5 months), respectively. Grade ≥3 treatment-emergent adverse events occurred in 88.2% and 85.7% of patients in cohorts 1 and 2, respectively. Safety was consistent with known profiles of single-agent niraparib and pembrolizumab.
Niraparib plus pembrolizumab showed clinical activity in patients with advanced and/or metastatic NSCLC.
The JASPER clinical trial studied a new combination treatment for advanced or metastatic non-small cell lung cancer (NSCLC). Pembrolizumab, a drug approved for NSCLC, was given with niraparib. Previous research showed that these 2 drugs together might work better than either drug alone. This study found that more than half of patients with high levels of a tumor marker responded to the combination, and one-fifth of patients with lower levels of the marker responded. The types of side effects from the combination were similar to side effects from both drugs alone. These results support more research on this combination.
聚（ADP-核糖）聚合酶（PARP）抑制剂可能与程序性细胞死亡受体-1（PD-1）抑制剂协同作用，增强适应性和先天抗肿瘤免疫反应。在 2 期 JASPER 研究（NCT04475939）中，评估了 PARP 抑制剂尼拉帕利联合 PD-1 抑制剂帕博利珠单抗治疗转移性和/或局部晚期非小细胞肺癌（NSCLC）患者。
肿瘤 PD-L1 肿瘤比例评分（TPS）≥50%（队列 1）或 1%-49%（队列 2）的患者接受一线尼拉帕利（200 mg 每日一次）联合帕博利珠单抗（200 mg 每 3 周一次）治疗。主要终点是研究者评估的客观缓解率（ORR）。次要终点包括缓解持续时间（DoR）、无进展生存期（PFS）、总生存期（OS）、安全性和药代动力学。
38 例患者入组队列 1 和 2。在队列 1 中，ORR（95%置信区间[CI]）为 56.3%（16 例患者中的 9 例；29.9%-80.2%）；16 例患者中有 2 例完全缓解，7 例部分缓解（PR）。在队列 2 中，ORR 为 20.0%（5.7%-43.7%），有 4 例 PR。在队列 1 和 2 中，中位 DoR 分别为 19.7 个月（95%CI，4.2 个月至不可估计[NE]）和 9.4 个月（95%CI，4.2 个月至 NE），中位 PFS 分别为 8.4 个月（95%CI，3.9-22.1 个月）和 4.2 个月（95%CI，2.0-6.2 个月），中位 OS 分别为 NE（95%CI，6.0 个月至 NE）和 7.7 个月（95%CI，4.0-12.5 个月）。队列 1 和 2 中分别有 88.2%和 85.7%的患者发生≥3 级治疗相关不良事件。安全性与尼拉帕利和帕博利珠单抗单药的已知特征一致。
尼拉帕利联合帕博利珠单抗在晚期和/或转移性 NSCLC 患者中显示出临床活性。
JASPER 临床试验研究了一种新的联合治疗方案，用于治疗晚期或转移性非小细胞肺癌（NSCLC）。帕博利珠单抗是一种已被批准用于 NSCLC 的药物，与尼拉帕利联合使用。先前的研究表明，这两种药物联合使用可能比单独使用任何一种药物效果更好。这项研究发现，超过一半的高水平肿瘤标志物患者对该联合治疗有反应，而五分之一的低水平标志物患者有反应。联合用药的副作用类型与两种药物单独使用的副作用类型相似。这些结果支持对这种联合用药进行更多的研究。
