Veliparib (Vel) in combination with chemoradiotherapy (CRT) of carboplatin/paclitaxel (C/P) plus radiation in patients (pts) with stage III non-small cell lung cancer (NSCLC) (M14-360/AFT-07).

• DOI: 10.1200/jco.2019.37.15_suppl.8510
• Publication Date: 2020-03-12T18:25:16Z
• Authors: David E. Kozono; Tom Stinchcombe; Joseph Kamel Salama; Jeffrey Bogart; William J. Petty; Michael J. Guarino; Lyudmila Bazhenova; James Mitchell La...; Jared Weiss; Thomas A. DiPetrillo; Steven J. Feigenberg; Beibei Hu; Silpa Nuthalapati; Yan Luo; Everett E. Vokes
• Keywords: Veliparib; Carboplatin; Clinical endpoint; Chemoradiotherapy

8510 Background: CRT is standard treatment (Tx) for pts with unresectable stage III NSCLC. Vel, a potent oral PARP1/2 inhibitor, interferes repair of chemotherapy- or radiation-induced DNA damage. In phase 2 study, Vel showed favorable efficacy vs placebo when added to C/P in IV The reported 1 trial assessed the safety and + C/P-based Tx NSCLC (NCT02412371). Methods: Eligible (≥18 yr, NSCLC, no prior therapy) received weekly C area under curve (AUC) P 45 mg/m 60 Gy (2 Gy/day) RT over 6–9 weeks (wk). was dose escalated from mg twice daily (BID) 240 BID followed by 120 consolidation therapy (CON) once every 3 wk AUC 6 200 cycles (cohort 1–5). Cohort CON. Samples pharmacokinetic (PK) analysis were collected on 4 day –3. primary endpoint establish recommended (RP2D) CRT/Vel Results: As Sep 2018, 48 enrolled into cohorts 1–6 at mg/120 (n = 7), 80 9), 8), 12), mg/240 5) CRT/CON; median age 65 yr (range, 48–81). PK proportional; 39 (81.3%) completed therapy. Grade ≥3 Tx-emergent adverse events (AEs) 37 (77.1%) pts; anemia febrile neutropenia (10.4% each) most common. Serious AEs observed 19 (39.6%) pts. Dose-limiting toxicities occurred 1; influenza pneumonia), insomnia), 2; neutropenia, thrombocytopenia, esophagitis, suprapubic pain, sepsis); CON chosen as maximum tolerated dose/RP2D. Of 41 evaluable tumor assessment, 26 (63.4%) had confirmed response. Interim progression-free survival 24.1 mo 8.9 – not reached); updated results will be reported. Conclusions: well promising antitumor activity determined RP2D. Clinical information: NCT02412371.