Related Experiment Video
Updated: Oct 21, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
JASPER: Phase 2 trial of first-line niraparib plus pembrolizumab in patients with advanced non-small cell lung cancer
Suresh S Ramalingam1, Eddie Thara2, Mark M Awad3
1Emory University, Winship Cancer Institute, Atlanta, Georgia.
Background:
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).
Methods:
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.
Results:
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.
Conclusions:
Niraparib plus pembrolizumab showed clinical activity in patients with advanced and/or metastatic NSCLC.
Lay Summary:
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.
Insights
The combination of niraparib and pembrolizumab demonstrated clinical activity in advanced non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression showed higher response rates to this PARP and PD-1 inhibitor combination.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- The combination of poly(ADP-ribose) polymerase (PARP) inhibitors and programmed cell death receptor-1 (PD-1) inhibitors may enhance antitumor immune responses.
- The JASPER study investigated the efficacy and safety of niraparib (a PARP inhibitor) plus pembrolizumab (a PD-1 inhibitor) in advanced non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To evaluate the clinical activity of first-line niraparib plus pembrolizumab in patients with metastatic and/or locally advanced NSCLC.
- To assess objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety of the combination therapy.
Main Methods:
- Phase 2 clinical trial (JASPER study) enrolling 38 patients with advanced NSCLC.
- Patients were divided into two cohorts based on PD-L1 tumor proportion score (TPS) ≥50% (cohort 1) or 1%-49% (cohort 2).
- Treatment consisted of niraparib (200 mg daily) plus pembrolizumab (200 mg every 3 weeks).
Main Results:
- Cohort 1 (PD-L1 ≥50%) showed an ORR of 56.3% (95% CI, 29.9%-80.2%), with 2 complete responses and 7 partial responses.
- Cohort 2 (PD-L1 1%-49%) had an ORR of 20.0% (95% CI, 5.7%-43.7%), with 4 partial responses.
- Median DoR, PFS, and OS varied between cohorts, with longer durations observed in cohort 1. Safety profiles were consistent with known data for single-agent niraparib and pembrolizumab.
Conclusions:
- Niraparib plus pembrolizumab demonstrated notable clinical activity in patients with advanced NSCLC.
- The combination warrants further investigation, particularly in patient populations with higher PD-L1 expression.
