1234P - A randomized, double-blind, Phase 2 trial of veliparib (ABT-888) with carboplatin and paclitaxel in previously untreated metastatic or advanced non...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Suresh Ramalingam
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors S.S. Ramalingam1, N. Blais2, J. Mazières3, M. Reck4, C.M. Jones5, E. Juhász6, L. Urban7, S. Orlov8, F. Barlesi9, E. Kio10, U. Keilholz11, Q. Qin12, J. Qian12, C. Nickner13, J. Dziubinski14, M.D. McKee15, V.L. Giranda16, V.A. Gorbunova17
  • 1Winship Cancer Institute, Emory University, 30322 - Atlanta/US
  • 2Oncology, Notre Dame du CHUM, H2L 4M1 - Montreal/CA
  • 3Department Of Pneumology, CHU Toulouse - Hôpital Larrey, 31400 - Toulouse/FR
  • 4Department Of Thoracic Oncology, Lung Clinic Grosshansdorf, Grosshansdorf/DE
  • 5Cancer And Blood Disorders, The Jones Clinic, 7710 Wolf River Circle - Germantown/US
  • 6Pulmonology Department Xiv, Koranyi National Institute of TB and Pulmonology, 1529 - Budapest/HU
  • 7Oncology, Mátra Gyógyintézet, Mátraháza/HU
  • 8Department Thoracic Oncology, Pavlov State Medical University, St.Petersburg/RU
  • 9Multidisciplinary Oncology & Therapeutic Innovatio, Hopital Nord, 13915 - Marseille CEDEX /FR
  • 10Center For Cancer Care, IU Health Goshen, Goshen/US
  • 11Charite, Charite, Campus Benjamin Franklin Medizinische Klinik III, 12200 - Berlin/DE
  • 12R436, AbbVie, 60064 - North Chicago/US
  • 138915, AbbVie, 60064 - North Chicago/US
  • 14R477, AbbVie, 60064 - North Chicago/US
  • 15Oncology Pharmaceutical Development, AbbVie, 60064 - North Chicago/US
  • 16Oncology Development, AbbVie, 60064 - North Chicago/US
  • 17Department Of Chemotherapy, Russian Research Oncology Center n.a. N. N. Blokhin Russian Cancer Research Center, Moscow/RU

Abstract

Aim

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 Ph 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, 90th event). 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. Adverse events (AE) in 20% or more pts 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% or more pts 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) 4.2 (3.1-5.6) 5.8 (4.2-6.1) 0.71 (0.50-1.13)
Squamous 4.1 (2.8-NA) 6.1 (5.8-8.3) 0.50 (0.24-1.04)
Non-squamous 5.0 (2.8-5.6) 4.3 (2.8-6.0) 0.94 (0.52-1.71)
OS (mo, 95% CI) 9.1 (5.4-12.3) 11.1 (8.8-13.4) 0.77 (0.50-1.18)
Squamous 8.5 (5.0-11.4) 10.3 (8.3-13.2) 0.75 (0.41-1.38)
Non-squamous 11.1 (4.8-NA) 12.6 (8.0-NA) 0.79 (0.43-1.47)
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 patient with squamous cell cancer (M11-089).

Disclosure

S.S. Ramalingam: Has served as a consultant on scientific advisory board meetings for AbbVie and has received honorarium; Q. Qin: AbbVie employee and stock owner; J. Qian: AbbVie employee and stock owner; C. Nickner: AbbVie employee and stock owner; J. Dziubinski: AbbVie employee and stock owner; M.D. McKee: AbbVie employee and stock owner; V.L. Giranda: AbbVie employee and stock owner. All other authors have declared no conflicts of interest.