Niraparib plus Dostarlimab in Pleural Mesothelioma or Non-Small Cell Lung Cancer harboring HRR mutations: interim results of the UNITO-001 phase 2 prospective trial

Introduction: Treatment of homologous recombination repair deficient (HRD)-tumours with PARP inhibitors has the potential to further increase tumour 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 HRR mutations. Methods: UNITO-001 is a phase 2, prospective, study aiming to investigate the combination of niraparib plus dostarlimab in pre-treated patients with HRD and programmed death ligand-1 (PD-L1) ≥ 1% NSCLC and/or PM. The primary endpoint is progression free survival (PFS). Results: A total of 17 out of 183 (10%) screened patients (12 MPM and 5 NSCLC) were included. The objective response rate (ORR) was 6% (95%CIs: 0.1-28.7) and the disease control rate (DCR) was 53% (95%CIs: 27.8-77). Median PFS was 3.1 (95%CIs: 2.7-N.A) and median overall survival (OS) was 4.2 (95%CIs 1.58-N.A) months. The PFS was 14.1 months in one PM patient harboring a germline BAP1 mutation. The treatment duration was 9.8 months in one PM patient harboring a somatic BRCA2 mutation. The most common adverse events (AEs) were grade 1-2 lymphopenia (59%), anemia (35%), hyponatremia (29%) and hypokalemia (29%). Grade ≥ 3 AEs were reported in 23% of the patients. Conclusion: 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 BAP1 somatic mutations. A potential antitumor activity emerged for PM with germline BAP1 and/or BRCA2 somatic mutations along with a good tolerability profile.