Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

• DOI: 10.1016/j.lungcan.2021.09.004
• Publication Date: 2021-09-17T15:01:39Z
• Authors: Jeffrey M. Clarke; Jyoti D. Patel; Francisco Robert; Ebenezer A. Kio; Eddie Thara; D. Ross Camidge; Martin Dunbar; Silpa Nuthalapati; Minh H. Dinh; Bruce A. Bach
• Keywords: Veliparib

Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and programmed death receptor-1 (PD-1) nivolumab CT have demonstrated encouraging efficacy for treatment non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated quadruple combination with in patients unresectable advanced/metastatic NSCLC.Patients were enrolled into five dosing cohorts: received 120 mg twice daily (BID) combined 360 mg, carboplatin AUC 6 mg/mL∙min, paclitaxel 200 mg/m2 (C/PAC) or 80/120/200/240 BID pemetrexed 500 (C/PEM). Primary objective was to identify recommended 2 dose (RP2D) + CT. Safety, tolerability, this also assessed.Twenty-five enrolled: C/PAC 19 (80-240 BID) C/PEM. No dose-limiting toxicities reported, RP2Ds C/PAC, 240 The most common any-grade adverse events (AEs) fatigue (56%), nausea (52%), anemia (48%). Grade 3/4 AEs included (32%) neutropenia (24%), frequent serious AE malignant neoplasm progression (12%). Veliparib exhibited approximately proportional kinetics range 80-240 C/PEM, no effects on pharmacokinetics. Overall, confirmed response rate 40%, best overall 64%.Veliparib tolerated NSCLC, evidence drug-drug interaction observed. Although preliminary, therapy may promising antitumor activity.