Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer

Jean Charles Soria, Egbert Smit, David Khayat, Benjamin Besse, Xinqun Yang, Cheng Pang Hsu, David Reese, Jeffrey Wiezorek, Fiona Blackhall

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Purpose: To determine the safety, pharmacokinetics (PK), and maximum-tolerated dose (MTD) up to a prespecified target dose of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab (PCB) in patients with previously untreated, nonsquamous, stage IIIb (with pleural effusion)/IV or recurrent non-small-cell lung cancer (NSCLC). Patients and Methods: In this phase 1b study, patients (n = 24) received PCB on day 1 of each 21-day cycle then dulanermin at 4 or 8 mg/kg/d for 5 consecutive days or 15 or 20 mg/kg/d for 2 consecutive days per assigned treatment cohort. Incidence of dose-limiting toxicities (DLTs), adverse events, and antidulanermin antibodies were assessed. PK parameters were recorded for each agent. Tumor response was measured by modified Response Evaluation Criteria in Solid Tumors. Results: Twenty-four patients received at least one dose of dulanermin plus PCB, six in each treatment cohort. There were no DLTs. An MTD was not reached, and the drug combination was well tolerated. Treatment-emergent adverse events were generally as expected for the PCB regimen. Adverse events attributed to dulanermin were grade 1/2; no significant hepatotoxicity occurred. There was minimal impact of PCB on the PK of dulanermin. There was one confirmed complete response and 13 confirmed partial responses. The overall response rate was 58% (95% CI, 37 to 78). Median progression-free survival was 7.2 months (95% CI, 4.7 to 10.3). Conclusion: Dulanermin plus PCB was well tolerated with no occurrence of DLTs and demonstrated antitumor activity in this patient population. Dulanermin at 8 mg/kg/d for 5 days and 20 mg/kg/d for 2 days every 3 weeks in combination with PCB is being studied in a phase II trial. © 2010 by American Society of Clinical Oncology.
    Original languageEnglish
    Pages (from-to)1527-1533
    Number of pages6
    JournalJournal of Clinical Oncology
    Volume28
    Issue number9
    DOIs
    Publication statusPublished - 20 Mar 2010

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