| General information |
| Database: | DB00778 |
| Objective: | Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In thisphase II study, they evaluated the activity and tolerability of ganetespib in previously treated patients with non small cell lung cancer (non small cell lung cancer). |
| Authors: | Socinski MA, et al |
| Title: | A multicenterphase II study of ganetespib monotherapy in patients with genotypically defined advanced non small cell lung cancer. |
| Journal: | Clin Cancer Res |
| Year: | 2013 |
| PMID: | 23553849 |
| Trial Design |
| Clinical Trial Id: | NCT01031225 |
| Agent: | ganetespib
|
| Target: | VEGFR, cMET, human epidermal growth factor receptor 2, IGFIR, EGFR, and other Hsp90 client proteins
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | A multicenterphase II study |
| Key Patients Feature: | progression free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. |
| Biomarker: | EGFR/KRAS mutations |
| Biomark Analysis: | all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCRbased assays (n = 3), in crizotinibna ve patients enrolled to cohort C. |
| Control Group Info: | cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). |
| Treatment Info: | Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by intravenous infusion once weekly for 3 weeks follotheyd by 1 week of rest, until disease progression. |
| Primary End Point: | progression free survival (PFS) at 16 weeks. |
| Secondary End Point: | objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. |
| Patients Number: | 99 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | in patients with ALKrearranged disease, with a response rate of 50% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.9 months [95% confidence interval (CI), 1.6-3.6] for cohort A, 1.9 months (95% CI, 1.6-3.7) for cohort B, and 1.8 months (95% CI, 1.8-2.9) for cohort C |
| Median OS A vs. C: | Median OS was 7.1 months (95% CI, 5.2-14.3), 11 months (95% CI, 3.9-17.1), and 8.8 months (95% CI, 4.4-10.5) for cohorts A, B and C, respectively |
| Adverse Event(agent arm): | The majority of drugrelated AEs were grade I and II and the overall incidence of grade III and IV was 29.3%. Gastrointestinal disorders comprised the majority of toxicities reported in nearly all patients (n = 92, 92.9%), including diarrhea (81.8%) and nausea (41.4%; |
| Conclusions: | Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced non small cell lung cancers, particularly in patients with tumors harboring ALK gene rearrangement. |