| General information |
| Database: | DB00065 |
| Objective: | non small cell lung cancer (non small cell lung cancer) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO1686) is an EGFR inhibitor active in preclinical models of EGFRmutated non small cell lung cancer with or without T790M. |
| Authors: | Sequist LV, et al |
| Title: | Rociletinib in EGFRmutated non small cell lung cancer |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 25923550 |
| Trial Design |
| Clinical Trial Id: | NCT01526928 |
| Agent: | rociletinib
|
| Target: | epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer harboring epidermal growth factor receptor mutations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase I/II |
| Key Patients Feature: | patients who had disease progression during previous treatment with an existing EGFR inhibitor.47 with the T790MP;17 withoutN |
| Biomarker: | T790Mpositive |
| Biomark Analysis: | 46 patients with T790Mpositive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790Mnegative disease who could be evaluated was 29% (95% CI, 8 to 51). |
| Control Group Info: | T790Mpositive vs T790Mnegative |
| Treatment Info: | In thisphase 12 study, they administered rociletinib to patients with EGFRmutated non small cell lung cancer who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790Mpositive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Treatment was administered in continuous 21day cycles. |
| Primary End Point: | assessment of safety, sideeffect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. |
| Secondary End Point: | NA |
| Patients Number: | 130 |
| Trial Results |
| DLT_MTD: | A maximum tolerated dose (the highest dose associated with a rate of doselimiting toxic effects of less than 33%) was not identified. The only common doselimiting adverse event was hyperglycemia |
| Objective Response Rate: | at 900 mg in its freebase form, or 500-1, 000 mg as a HBr saltP vs N ORR:59% vs 29% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 13.1 vs 5.6(P vs N) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | hyperglycaemia(36%); |
| Conclusions: | Rociletinib was active in patients with EGFRmutated non small cell lung cancer associated with the T790M resistance mutation |