Safety and efficacy of Cisplatin in combination with Sintilimab and Niraparib in patients with advanced solid tumors:...

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.

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.

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/m², 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, P = 0.032) and OS (14.97 months, P = 0.036) compared to those with PD-L1 expression < 1%.

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.

https://www.chictr.org.cn/; ID: ChiCTR1900024488.