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my personal edition > lung cancer > news
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DGDispatch
Novel Treatment Shows Activity in Relapsed, Refractory NSCLC Patients: Presented at AACR-NCI-EORTC
By Crina Frincu-Mallos, PhD
SAN FRANCISCO, CA -- November 1, 2007 -- There is promising evidence of biologic activity of a novel heat shock protein 90 (Hsp90) inhibitor, IPI-504, in a heavily pre-treated patient population with Stage 4 non-small cell lung cancer (NSCLC), researchers reported here at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.
IPI-504 is part of a class of water-soluble Hsp90 inhibitors, currently studied in several different clinical trials, said the lead author, Lecia V. Sequist, MD, MPH, Haematology and Oncology Division, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States.
Dr. Sequist discussed the results here in a poster presentation on behalf of a research team from Massachusetts General Hospital, Dana Farber Cancer Institute, and Infinity Pharmaceuticals, Inc.
Preliminary data from the other phase 1 clinical trial of IPI-504, tested in patients with imatinib-resistant metastatic gastrointestinal stromal tumours (GIST), were presented at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting this past June.
The scientific rationale behind the evaluation of IPI-504 in this patient population was matched by a significant unmet medical need to find effective treatments for NSCLC patients that acquire resistance to erlotinib or gefitinib, according to Dr. Sequist and collaborators.
The aim of this phase 1 study was to evaluate the toxicity and find the maximum tolerated dose (MTD) in patients who have failed treatment with tyrosine kinase inhibitors, explained Dr. Sequist.
A total of 11 patients (male to female ratio 2:9), average age 63.6 years participated in this trial. All patients had Stage 4 NSCLC at screening.
The epidermal growth factor receptor (EFGR) status was known for all patients: out of ten evaluable patients, nine had the EGFR mutation, while one had EGFR wild type. EFGR plays an important role in the pathogenesis of NSCLC, noted Dr. Sequist, and is highly sensitive to IPI-504.
IPI-504 was given intravenously in a 30-minute infusion twice weekly during a 4-week cycle.
The investigational agent was tested at three dose levels: 150 mg/m2 (n = 3), 225 mg/m2 (n = 4), and 300 mg/m2 (n = 5).
Evidence of biologic activity was assessed using PET imaging.
The dose-limiting toxicities observed were grade 3 fatigue (n = 2), grade 3 hypokalemia (n = 1), and hypophosphatemia (n = 1), observed at the 300 mg/m2 dose level. Fatigue and back pain were the most common adverse events (AEs) across all grades AEs.
A total of seven patients had stable disease (SD) as best response. One of these patients, who had progressed after treatment with three different tyrosine kinase inhibitors, has had a SD response with IPI-504 for more than 27 weeks and is now receiving her 7th cycle of treatment, said Dr. Sequist.
"IPI-504 has been well tolerated and has displayed promising signs of biological activity in this heavily pretreated patient population," commented Dr. Sequist.
The recommended dosing schedule for the phase 2 subsequent trial is 400 mg/m2 for 2 weeks, followed by a 10-day "drug holiday", based on observed patient noncompliance with the previous schedule.
According to Dr. Sequist and colleagues, the additional phase 2 portion of the study is planned to start accruing patients with advanced NSCLC by the end of 2007.
Funding for this study was provided by Infinity Pharmaceuticals, Inc., and MedImmune.
[Presentation title: Phase I/II trial of the novel Hsp90 inhibitor, IPI-504, in patients with relapsed and/or refractory stage IIIB or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status. Abstract B79]
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