| General information |
| Database: | DB00842 |
| Objective: | XL647 is an oral smallmolecule inhibitor of multiple receptor tyrosine kinases, including endothelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2, human epidermal growth factor receptor 2 and Ephrin typeB receptor 4 (EphB4). they undertook an openlabel, multiinstitutionalphase II study to investigate the efficacy and safety of XL647 in treatmentnaive non small cell lung cancer patients clinically enriched for the presence of EGFR mutations. |
| Authors: | Pietanza MC, et al |
| Title: | Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non small cell lung cancer. |
| Journal: | J Thorac Oncol. |
| Year: | 2012 |
| PMID: | 22722787 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | XL647
|
| Target: | endothelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2, human epidermal growth factor receptor 2 and Ephrin typeB receptor 4 (EphB4)
|
| 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: | Phase II study |
| Key Patients Feature: | Eligibility included patients with advancedstage treatmentnaive lung adenocarcinoma with a known sensitizing mutation of EGFR or patients with at least one of the following criteria: being Asian, female, or having minimal or no smoking history. |
| Biomarker: | EGFR mutation status |
| Biomark Analysis: | Thirtyeight patients (69%) had material available for mutation testing and 14 EGFRsensitizing mutations were detected. The response rate and progression free survival for EGFRmutationpositive patients were 57% (8/14) and 9.3 months (90% confidence interval, 5.511.7). |
| Control Group Info: | single arm |
| Treatment Info: | Two dosing schedules were evaluated; in the "intermittent 5 & 9 dosing" cohort, XL647 350 mg for 5 days every 14 days was given; and in the "daily dosing" cohort, XL647 300 mg daily for 28 days was administered. |
| Primary End Point: | confirmed objective response rate. |
| Secondary End Point: | NA |
| Patients Number: | 41 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 20% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.3 months (90% confidence interval, 3.76.7) |
| Median OS A vs. C: | 19.3 months (90% CI, 18.4-23.3). |
| Adverse Event(agent arm): | NA |
| Conclusions: | XL647 administered on an intermittent or dailydosing schedule demonstrated antitumor activity in patients with EGFRactivating mutations. The adverseevent profile was similar for the two dosing schedules. |