Durvalumab (D) in combination with olaparib (O) for advanced, previously treated non-small cell lung cancer (NSCLC).

• DOI: 10.1200/jco.2022.40.16_suppl.e21153
• Publication Date: 2022-06-06T17:21:07Z
• Authors: Daniel Desmond; Rasa Vilimas; Cristina Mullenix; Chen Zhao; Eva Szabo; Meenakshi Shelat; Madison Ballman; Susan Sansone; Seth M. Steinberg; Jung-Min Lee; Arun Rajan
• Keywords: Olaparib

e21153 Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) show variable clinical activity in individuals with advanced cancers. In the lung-MAP substudy S1400G, talazoparib alone was not sufficiently active squamous lung cancers homologous recombinant repair deficiency. Combinations of PARPi immune checkpoint (ICIs) are under investigation since preclinical studies an immunostimulatory effect that can potentially increase responsiveness to ICIs. To test this hypothesis, we evaluated PARPi, O ICI, D NSCLC who had received at least one prior platinum-based regimen. Methods: Eligible participants were enrolled expansion cohort a proof-of-concept phase I/II study (NCT02484404) and 300 mg PO BID 1500 IV every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint progression-free survival (PFS). Results: Between July 2016 2021, 15 recurrent (median age: 66 years; stage IV: 12; adenocarcinoma 11; ICI: 9). After median potential follow-up 39.6 months (mo), PFS (mPFS) 3.2 mo (95% CI: 0.9-7.6). Among 14 subjects known EGFR mutation status, mPFS longer 11 EGFR-WT tumors (5.7 vs. 0.9 mo; p = 0.001). DNA ( APC, BAP1, BRCA1, BRCA2, CHEK2, FANCI, FANCL PALB2) status for 9 subjects; (n 7) without 2) mutations 18.1 (p 0.68), respectively. Tumor PD-L1 expression > 50% 3/10) ICI therapy 9/15) associated longer, albeit statistically significant, mPFS: 7.6 1.8 0.22, 5.7 0.39, Two (13%) partial responses, 7 (47%) stable 6 (40%) cases progressive observed. Four (27%) subjects, including 3 previously treated ICIs, achieved durable response stability up years. Treatment-related adverse events (TRAEs) generally mild (grade 1 2). most common TRAEs anemia (40%), thrombocytopenia (27%), anorexia, fatigue, pain, hypophosphatemia (each observed 20%). Grade occurred (all hematologic). Immune-related AEs individuals. developed myelodysplasia after 12 36 treatment. Three (20%) required dose reductions discontinuation due anemia. There no treatment-related deaths. Accrual will continue 20 eligible enrolled. Conclusions: O+D has acceptable safety modest efficacy unselected population NSCLC. Sufficient is EGFR-mutated tumors. Genomic immunological analyses being performed identify predictive biomarkers benefit be reported. Clinical trial information: NCT02484404.