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.
Blackhall, Fiona H
AffiliationService des Innovations, Thérapeutiques Précoces, Département de Médecine, Institut Gustave Roussy, Villejuif, France. firstname.lastname@example.org
MetadataShow full item record
AbstractPURPOSE: 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.
CitationPhase 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. 2010, 28 (9):1527-33 J Clin Oncol
JournalJournal of Clinical Oncology
- Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer.
- Authors: Soria JC, Márk Z, Zatloukal P, Szima B, Albert I, Juhász E, Pujol JL, Kozielski J, Baker N, Smethurst D, Hei YJ, Ashkenazi A, Stern H, Amler L, Pan Y, Blackhall F
- Issue date: 2011 Nov 20
- A phase 1B study of dulanermin in combination with modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer.
- Authors: Wainberg ZA, Messersmith WA, Peddi PF, Kapp AV, Ashkenazi A, Royer-Joo S, Portera CC, Kozloff MF
- Issue date: 2013 Dec
- FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer.
- Authors: Cohen MH, Gootenberg J, Keegan P, Pazdur R
- Issue date: 2007 Jun
- A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
- Authors: Herbst RS, Hammond LA, Carbone DP, Tran HT, Holroyd KJ, Desai A, Williams JI, Bekele BN, Hait H, Allgood V, Solomon S, Schiller JH
- Issue date: 2003 Sep 15
- Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer.
- Authors: Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F
- Issue date: 2004 Jun 1