| General information |
| Database: | DB00818 |
| Objective: | IPI504 is a novel, watersoluble, potent inhibitor of heatshock protein 90 (Hsp90). Its potential anticancer activity has been validated in preclinical in vitro and in vivo models. they studied the activity of IPI504 after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced, molecularly defined non small cell lung cancer (non small cell lung cancer). |
| Authors: | Sequist LV, et al |
| Title: | Activity of IPI504, a novel heatshock protein 90 inhibitor, in patients with molecularly defined non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20940188 |
| Trial Design |
| Clinical Trial Id: | NCT00431015 |
| Agent: | IPI504
|
| Target: | Heat shock protein HSP 90
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | prospective, nonrandomized, multicenter, phase II study of IPI504 monotherapy |
| Key Patients Feature: | Patients with advanced non small cell lung cancer, prior treatment with EGFR TKIs, and tumor tissue available for molecular genotyping were enrolled |
| Biomarker: | EGFR/ALK mutation |
| Biomark Analysis: | Although both EGFR groups were below the target ORR of 20%, among the three patients with an ALK gene rearrangement, two had partial responses and the third had prolonged stable disease (7.2 months, 24% reduction in tumor size). |
| Control Group Info: | single arm |
| Treatment Info: | Treatment consisted of a 30minute infusion of intravenous IPI504 on days 1, 4, 8, and 11 of a 21day cycle. Therapy continued until progressive disease, intolerable adverse effects, or elective withdrawal. |
| Primary End Point: | objective response rate (ORR). |
| Secondary End Point: | safety, progression free survival (PFS), and analysis of activity by molecular subtypes. |
| Patients Number: | 76 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 7% (five of 76) overall, 10% (four of 40) in EGFR wildtype patients and 4% (one of 28) in EGFR mutants. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.86 months (95% CI, 2.43 to 4.18 months) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most adverse events were grades 1 or 2; nine patients (12%) had dose reductions for toxicity, while 11 (14%) discontinued therapy for adverse events. The most commonly reported adverse events (regardless of relationship to drug) were fatigue, nausea, diarrhea, vomiting, cough, anorexia, and joint/muscle aches |
| Conclusions: | IPI504 has clinical activity in patients with non small cell lung cancer, particularly among patients with ALK rearrangements. |