Data from Niraparib plus Dostarlimab in Pleural Mesothelioma or Non–Small Cell Lung Cancer Harboring <i>HRR</i> Mutations: Interim Results of the UNITO-001 Phase II Prospective Trial

Abstract

<div>AbstractPurpose:<p>Treatment of homologous recombination repair–deficient (HRD)-tumors with PARP inhibitors has the potential to further increase tumor immunogenicity, suggesting a synergistic effect with immunotherapy. Here we present the preliminary results of niraparib in combination with dostarlimab for pleural mesothelioma (PM) or non–small cell lung cancer (NSCLC) harboring <i>HRR</i> mutations.</p>Patients and Methods:<p>UNITO-001 is a phase II, prospective, study aiming to investigate the combination of niraparib plus dostarlimab in pretreated patients with HRD and programmed death ligand-1 (PD-L1) ≥1% NSCLC and/or PM. The primary endpoint is progression-free survival (PFS).</p>Results:<p>Seventeen of 183 (10%) screened patients (12 PM and 5 NSCLC) were included. The objective response rate (ORR) was 6% [95% confidence interval (CI): 0.1–28.7] and the disease control rate (DCR) was 53% (95% CI: 27.8–77). Median PFS was 3.1 (95% CI: 2.7–N.A) and median overall survival (OS) was 4.2 (95% CI: 1.58–NA) months. The PFS was 14.1 months in one PM patient harboring a germline <i>BAP1</i> mutation. The treatment duration was 9.8 months in one PM patient harboring a somatic <i>BRCA2</i> mutation. The most common adverse events (AE) were grade 1–2 lymphopenia (59%), anemia (35%), hyponatremia (29%), and hypokalemia (29%). Grade ≥3 AEs were reported in 23% of the patients.</p>Conclusions:<p>This preliminary analysis highlighted the lack of antitumor activity for the combination of niraparib and dostarlimab in patients with PM and/or advanced NSCLC harboring <i>BAP1</i> somatic mutations. A potential antitumor activity emerged for PM with germline <i>BAP1</i> and/or <i>BRCA2</i> somatic mutations along with a good tolerability profile.</p></div>