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
Mené sur 17 patients atteints d'un mésothéliome pleural ou d'un cancer du poumon non à petites cellules avec mutations au niveau du gène HRR, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du niraparib en combinaison avec le dostarlimab
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.