Preclinical evidence has suggested that Niraparib ( Zejula ), a poly (ADP-ribose) polymerase inhibitor, may synergise with PD-1 inhibitors.
Pembrolizumab ( Keytruda ) is a PD-1 inhibitor approved as first-line treatment for patients with advanced non-small cell lung cancer ( NSCLC ) with a programmed death ligand 1 ( PD-L1 ) tumour proportion score ( TPS ) greater than or equal to 1%.
The phase II JASPER study is assessing efficacy and safety of first-line Niraparib plus PD-1 inhibitor in patients with NSCLC.
Researchers have reported data from patients who received Niraparib plus Pembrolizumab.
Chemotherapy-naïve patients with locally advanced / metastatic NSCLC, no known EGFR-sensitising mutations and/or ALK or ROS1 translocations, and no prior PD-(L)1 therapy were stratified by PD-L1 TPS: greater than or equal to 50% ( Cohort 1 ), 1–49% ( Cohort 2 ).
Patients received Pembrolizumab 200 mg every 3 weeks intravenously and Niraparib 200 mg/day orally.
Primary endpoint was investigator-assessed confirmed objective response rate ( ORR ) per RECIST v1.1 in patients with 1 or more post-baseline scan ( modified intent-to-treat [ mITT ] population ).
Secondary endpoints ( assessed in mITT ) were duration of response ( DoR ), progression-free survival ( PFS ), and safety ( in patients who received 1 or more dose of study drug ).
A total of 17 and 21 patients were enrolled in Cohorts 1 and 2, respectively; 1 patient in each cohort withdrew consent before baseline scan ( mITT, n=16 and n=20, respectively ).
In Cohort 1, confirmed ORR ( 95% CI ) was 56.3% ( 29.9–80.2 ) with 2 complete responses.
In Cohort 2, confirmed ORR ( 95% CI ) was 20% ( 5.7–43.7 ).
Median progression-free survival was 8.4 months ( Cohort 1: 95% CI: 3.9–22.1; n=16 ) and 4.2 ( Cohort 2: 95% CI: 2.0–6.2; n=20 ).
Median duration of response was 19.7 months ( Cohort 1: 95% CI: 4.2–NE [ not-estimable ] ; n=9 ) and 9.4 ( Cohort 2: 95% CI: 4.2–15.1; n=4 ).
Overall survival data were immature.
The most frequent grade 3 or more treatment-emergent adverse events ( more than 10% both cohorts ) were anaemia ( 24% Cohort 1; 29% Cohort 2 ), pneumonia ( 24% Cohort 1; 14% Cohort 2 ), and fatigue ( 12% Cohort 1; 14% Cohort 2 ).
In conclusion, Niraparib plus Pembrolizumab has induced durable responses in patients with non-small cell lung cancer, with larger effects in the PD-L1–high cohort.
The combination has shown no new safety signals. ( Xagena )
Source: European Society for Medical Oncology ( ESMO ) Virtual Meeting, 2020