Safety and efficacy of Cisplatin in combination with Sintilimab and Niraparib in patients with advanced solid tumors: A phase Ib study.
[BACKGROUND] Immune checkpoint inhibitors combined with PARP inhibitors and chemotherapy can enhance anti-tumor activity.
- 95% CI 36.92-76.65
- 추적기간 47.9 months
APA
Tao H, Liu Y, et al. (2026). Safety and efficacy of Cisplatin in combination with Sintilimab and Niraparib in patients with advanced solid tumors: A phase Ib study.. Cancer pathogenesis and therapy, 4(1), 41-50. https://doi.org/10.1016/j.cpt.2025.08.005
MLA
Tao H, et al.. "Safety and efficacy of Cisplatin in combination with Sintilimab and Niraparib in patients with advanced solid tumors: A phase Ib study.." Cancer pathogenesis and therapy, vol. 4, no. 1, 2026, pp. 41-50.
PMID
41394111
Abstract
[BACKGROUND] Immune checkpoint inhibitors combined with PARP inhibitors and chemotherapy can enhance anti-tumor activity. This phase Ib clinical study was designed to evaluate the safety and efficacy of cisplatin in combination with sintilimab and niraparib in patients with advanced solid tumors.
[METHODS] Patients with advanced solid tumors who had progressed after one or more lines of standard therapy were enrolled in the study, and received cisplatin and sintilimab on day 1 and niraparib from days 1-21 every 3 weeks for up to 4 cycles, followed by maintenance therapy with sintilimab and niraparib (the same doses and schedules as before), until disease progression, death, or intolerable toxicities. During the dose-escalation phase, patients were divided into three dose groups on the basis of a 3 + 3 dose-escalation regimen, and a dose-expansion phase was conducted based on the determined maximum tolerated dose (MTD). The primary endpoint was safety, including treatment-related adverse events (TRAEs), dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D), and the secondary endpoint was efficacy. In addition, exploratory endpoints were prespecified to analyze potential biomarkers.
[RESULTS] From July 31, 2019, to July 1, 2022, a total of 26 patients were enrolled, and no DLTs were observed in the dose-escalation phase. The recommended RP2Ds of cisplatin, sintilimab, and niraparib were 60 mg/m, 200 mg, and 100 mg every 3 weeks, respectively. All patients experienced TRAEs of varying severity, and a 19.23% (5 patients) incidence of immune-related adverse events (irAEs). With the median follow-up time of 47.9 months (95% CI: 38.8-NA), objective response rate was 26.92% (7 patients, 95% confidence interval [CI], 11.57-47.79), disease control rate was 57.69% (15 patients, 95% CI: 36.92-76.65), the median progression-free survival (PFS) was 3.30 months (95% CI: 2.14-4.46) and the median overall survival (OS) was 8.03 months (95% CI: 3.41-12.66), with PFS rates of 26.92% (seven patients) and 11.54% (three patients) at 6 and 12 months, and OS rates of 69.23%, 34.62% and 11.54% at 6, 12 and 24 months, respectively. Patients with programmed cell death ligand 1 (PD-L1) expression ≥ 1% showed significantly longer PFS (3.93 months, = 0.032) and OS (14.97 months, = 0.036) compared to those with PD-L1 expression < 1%.
[CONCLUSION] The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in patients with advanced solid tumors. Further validation in larger, histology-specific patients is needed to confirm clinical benefit.
[TRIAL REGISTRATION] https://www.chictr.org.cn/; ID: ChiCTR1900024488.
[METHODS] Patients with advanced solid tumors who had progressed after one or more lines of standard therapy were enrolled in the study, and received cisplatin and sintilimab on day 1 and niraparib from days 1-21 every 3 weeks for up to 4 cycles, followed by maintenance therapy with sintilimab and niraparib (the same doses and schedules as before), until disease progression, death, or intolerable toxicities. During the dose-escalation phase, patients were divided into three dose groups on the basis of a 3 + 3 dose-escalation regimen, and a dose-expansion phase was conducted based on the determined maximum tolerated dose (MTD). The primary endpoint was safety, including treatment-related adverse events (TRAEs), dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D), and the secondary endpoint was efficacy. In addition, exploratory endpoints were prespecified to analyze potential biomarkers.
[RESULTS] From July 31, 2019, to July 1, 2022, a total of 26 patients were enrolled, and no DLTs were observed in the dose-escalation phase. The recommended RP2Ds of cisplatin, sintilimab, and niraparib were 60 mg/m, 200 mg, and 100 mg every 3 weeks, respectively. All patients experienced TRAEs of varying severity, and a 19.23% (5 patients) incidence of immune-related adverse events (irAEs). With the median follow-up time of 47.9 months (95% CI: 38.8-NA), objective response rate was 26.92% (7 patients, 95% confidence interval [CI], 11.57-47.79), disease control rate was 57.69% (15 patients, 95% CI: 36.92-76.65), the median progression-free survival (PFS) was 3.30 months (95% CI: 2.14-4.46) and the median overall survival (OS) was 8.03 months (95% CI: 3.41-12.66), with PFS rates of 26.92% (seven patients) and 11.54% (three patients) at 6 and 12 months, and OS rates of 69.23%, 34.62% and 11.54% at 6, 12 and 24 months, respectively. Patients with programmed cell death ligand 1 (PD-L1) expression ≥ 1% showed significantly longer PFS (3.93 months, = 0.032) and OS (14.97 months, = 0.036) compared to those with PD-L1 expression < 1%.
[CONCLUSION] The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in patients with advanced solid tumors. Further validation in larger, histology-specific patients is needed to confirm clinical benefit.
[TRIAL REGISTRATION] https://www.chictr.org.cn/; ID: ChiCTR1900024488.