102PD - A randomized, double-blind, phase 2 trial of veliparib (ABT-888) with carboplatin and paclitaxel in previously untreated metastatic or advanced non-...

Date 16 April 2015
Event ELCC 2015
Session Medical and radiation oncology
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Julien Mazieres
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors J. Mazieres1, N. Blais2, E. Juhasz3, L. Urban4, S. Orlov5, Q. Qin6, M. McKee7, V. Giranda7, V. Gorbunova8, S.S. Ramalingam9
  • 1Thoracic Oncology, CHU Toulouse, Hôpital de Larrey, 31059 - Toulouse/FR
  • 2Hematology-oncology, Notre Dame du CHUM, Montreal/CA
  • 3Oncology, National Koranyi Institute of Pulmonology, Budapest/HU
  • 4Oncology, Matrahaza University and Teaching Hospital, 3233 - Matrahaza/HU
  • 5Oncology, Pavlov State Medical University, St. Petersburg/RU
  • 6Data And Statistical Sciences, AbbVie, North Chicago/US
  • 7Global Pharmaceutical R&d, AbbVie, North Chicago/US
  • 8Oncology, Institution of Russian Academy of Medical Science, Moscow/RU
  • 9Hematology & Medical Oncology, Emory University Winship Cancer Institute, 30322 - Atlanta/US

Abstract

Aim/Background

Platinum-based regimens are the current standard of care for patients (pts) with metastatic non-small cell lung cancer (NSCLC). Veliparib (V) is a potent, orally bioavailable PARP inhibitor that (1) enhances the efficacy of platinum-containing DNA damaging therapies in preclinical models, and (2) has been safely combined with full dose carboplatin (C) and paclitaxel (P) in Phase 1 trials.

Methods

Pts with advanced or metastatic NSCLC were randomized 2:1 to V at 120 mg BID or placebo plus CP. Pts were stratified by histology and smoking history. The primary endpoint was progression-free survival (PFS, with 80% power and α = 0.05, assuming log-rank HR of 0.51). All data analyses were performed at the 78th PFS event except overall survival (OS, final as of Nov 6, 2014). In the case of a positive signal, continuation of the program to a Phase 3 trial was planned.

Results

158 pts were randomized; 64% of pts were male; 49% had squamous NSCLC; 60% smoked within 1 year of study entry. Preliminary veliparib PK from 102 VCP pts: the steady-state veliparib Cmax was 1.0 ± 0.4 µg/mL, and the AUC0-12 was 6.4 ± 2.7 µg*h/mL on Day 3 of Cycle 1 (comparable exposures regardless of smoking history). Adverse events (AE) occurring in ≥20% of patients were alopecia (39% VCP/42% CP), anemia (31/42), neutropenia (36/29), nausea (28/25) and peripheral neuropathy (24/25). Leukopenia was seen in 11% VCP vs. 1% CP. Grade 3/4 AEs in 10% were neutropenia (23/19) and anemia (10/10). Mean chemo cycles were 4.5 C/4.5 P with CP and 4.5 C/4.3 P with VCP.

Efficacy (ITT Population)

CP, n = 53 VCP, n = 105 HR VCP/CP
PFS (mo, 95% CI) Squamous Non-squamous 4.2 (3.1-5.6) 4.1 (2.8-NA) 5.0 (2.8-5.6) 5.8 (4.2-6.1) 6.1 (5.8-8.3) 4.3 (2.8-6.0) 0.71 (0.50-1.13) 0.50 (0.24-1.04) 0.94 (0.52-1.71)
OS (mo, 95% CI) Squamous Non-squamous 9.1 (5.4-12.3) 8.4 (5.0-12.9) 11.1 (4.8-13.2) 11.7 (8.8-13.7) 10.3 (8.3-13.2) 12.8 (8.0-17.2) 0.80 (0.54-1.18) 0.73 (0.43-1.24) 0.90 (0.51-1.58)
Overall Response Rate (%, 95% CI) 28 (17-42) 31 (22-40) —–
Duration Of Response (mo, 95% CI) 3.3 (2.7-4.3) 6.9 (4.4-7) 0.11 (0.03-0.50)

Conclusions

Estimated HR for progression and death from NSCLC favored VCP over CP, but results were not statistically significant. VCP was delivered without excessive toxicity. Based on results in the squamous histology subgroup, a Phase 3 pivotal trial has been initiated for patients with squamous cell cancer (M11-089).

Clinical trial identification NCT01560104

Disclosure

Q. Qin, M. McKee and V. Giranda: AbbVie employee and stock owner.

All other authors have declared no conflicts of interest.