Abstract 1268P
Background
Preclinical evidence suggests niraparib (nira), a poly (ADP-ribose) polymerase inhibitor, may synergise with PD-1i. Pembrolizumab (pembro) is a PD-1i approved as 1L treatment for patients with advanced NSCLC with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥1%. The phase II JASPER study (NCT03308942) assesses efficacy and safety of 1L nira plus PD-1i in patients with NSCLC. Here, we report data from patients who received nira plus pembro.
Methods
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: ≥50% (Cohort 1), 1%–49% (Cohort 2). Patients received pembro 200 mg every 3 weeks intravenously and nira 200 mg/day orally. Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1 in patients with ≥1 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 dose of study drug).
Results
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). PFS and DoR are shown in the table; overall survival data were immature. The most frequent Grade ≥3 treatment-emergent adverse events (>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). Table: 1268P
Secondary efficacy outcomes assessed in mITT population (median PFS) and mITT population with confirmed CR/PR (median DoR)
| Cohort 1 (PD-L1 ≥50%) | Cohort 2 (PD-L1 1%–49%) | |
| Median DoR, months (95% CI) | 19.7 (4.2–NE) n=9 | 9.4 (4.2–15.1) n=4 |
| Median PFS, months (95% CI) | 8.4 (3.9–22.1) n=16 | 4.2 (2.0–6.2) n=20 |
CI, confidence interval; CR, complete response; DoR, duration of response; mITT, modified intent-to-treat; NE, not estimable; PD-L1, programmed death ligand 1; PFS, progression-free survival; PR, partial response.
Conclusions
Nira plus pembro induces durable responses in patients with NSCLC, with larger effects in the PD-L1–high cohort. The combination shows no new safety signals.
Clinical trial identification
NCT03308942.
Editorial acknowledgement
Medical writing support was provided by Emily Mercadante, PhD, and Gemma Corr, DPhil, Fishawack Indicia Ltd, UK, funded by GSK.
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline (GSK; study 213352).
Disclosure
S.S. Ramalingam: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy: AbbVie; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Genteelness/Roche; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Advaxix. M.M. Awad: Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Lilly; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Achilles; Advisory/Consultancy: AbbVie. A. Dowlati: Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Tesaro; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Vertex; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): United Therapeutics; Research grant/Funding (institution): Mirati; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Incuron; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Ariad; Research grant/Funding (institution): Bayer. T. Stinchcombe: Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly Oncology; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Advaxis; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Merck. G.K. Dy: Honoraria (self), Advisory/Consultancy: GlaxoSmithKline. D.R. Spigel: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Moderna Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Nektar; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy: TRM Oncology; Advisory/Consultancy: Precision Oncology; Advisory/Consultancy: Evelo Therapeutics; Advisory/Consultancy: Illumina; Advisory/Consultancy: PharmaMar; Research grant/Funding (institution): University of Texas Southwestern Medical Center - Simmons Cancer Center; Research grant/Funding (institution): G1 Therapeutics ; Research grant/Funding (institution): Neon Therapeutics; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): GRAIL; Research grant/Funding (institution): Transgene; Research grant/Funding (institution): Aeglea Biotherapeutics ; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Ipsen; Advisory/Consultancy: Aptitude Health; Advisory/Consultancy: Bayer ; Advisory/Consultancy: Dracen Pharmaceuticals ; Advisory/Consultancy: Iksuda Therapeutics ; Advisory/Consultancy: Molecular Templates; Advisory/Consultancy: Seattle Genentics; Advisory/Consultancy: TRIPTYCH Health Partners; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): BIND Therapeutics; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): ImClone Systems; Advisory/Consultancy: Intellisphere; Advisory/Consultancy, Research grant/Funding (institution): GSK. L. Evilevitch: Shareholder/Stockholder/Stock options, Full/Part-time employment: GlaxoSmithKline. Y. Tang: Shareholder/Stockholder/Stock options, Full/Part-time employment: GlaxoSmithKline. I. Teslenko: Shareholder/Stockholder/Stock options, Full/Part-time employment: GlaxoSmithKline. All other authors have declared no conflicts of interest.