Randomized phase III trial of gemcitabine/carboplatin with or without iniparib (BSI-201) in patients with previously untreated stage IV squamous non-small cell lung cancer (NSCLC).

Abstract

TPS220 Background: Recent advances in the treatment of NSCLC, including bevacizumab and pemetrexed, have been limited to patients with non-squamous cancers because of concerns of safety and efficacy. Poly (ADP-ribose) polymerase-1 (PARP1) is a critical DNA repair enzyme, and is significantly upregulated at the mRNA level in multiple cancer types, including squamous cell lung cancer. Iniparib is a novel agent with PARP1 inhibitory activity and has demonstrated synergistic activity with gemcitabine and carboplatin in preclinical studies. This phase III study will compare the results of treatment with the gemcitabine/carboplatin doublet alone or in combination with iniparib. The primary endpoint is overall survival. Methods: Trial Design: Patients are randomized 1:1 to Arm A (with iniparib) or Arm B (without iniparib). All patients receive gemcitabine 1000 mg/m2 IV days 1 and 8, and carboplatin AUC=5 IV on day 1 of each 21-day cycle. Arm A patients also receive iniparib 5.6 mg/kg IV on days 1, 4, 8, and 11. All patients are assessed for response per RECIST version 1.1 every 6 weeks. While 6 treatment cycles are planned, patients without evidence of progression or other reason for discontinuation may remain on treatment beyond 6 cycles. Accrual of 825 patients provides 90% power to detect an improvement in survival from 8 months (anticipated with gemcitabine/carboplatin) to 10.7 months. Eligibility: Patients with newly diagnosed stage IV (M1a and M1b) squamous NSCLC with ECOG PS 0-1 are eligible, including those with disseminated metastases or malignant pleural or pericardial effusions. Patients may have had carboplatin in the adjuvant setting for early stage disease, but prior treatment with gemcitabine or iniparib is not allowed. Additional exclusion criteria include: history of recent cardiac disease, untreated brain metastases, and treatment for early-stage lung cancer within 12 months of study entry. There are currently 167 patients enrolled with a total of 825 planned in this international multi-center trial.