| General information |
| Database: | DB00131 |
| Objective: | TGF¦Â signaling plays a key role in tumor progression, including malignant glioma. Smallmolecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGF¦Â signaling and reduce tumor progression in preclinical models. They investigated its properties in a firstinhuman dose (FHD) study in patients with cancer. |
| Authors: | Rodon J, et al |
| Title: | Firstinhuman dose study of the novel transforming growth factor¦Â receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. |
| Journal: | Clin Cancer Res. |
| Year: | 2015 |
| PMID: | 25424852 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | LY2157299
|
| Target: | TGFbeta receptor type I
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advenced solid tumours |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I firstinhuman dose study |
| Key Patients Feature: | Eligible patients must have progressed on prior effective therapies and had a histologic or cytologic diagnosis of a malignancy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). |
| Primary End Point: | DLT, MDT, DCR and toxcity |
| Secondary End Point: | NA |
| Patients Number: | 65 |
| Trial Results |
| DLT_MTD: | the intermittent administration of LY2157299 at 300 mg/day is safe |
| Objective Response Rate: | NA |
| Disease Control Rate: | In part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD more than and equal to 6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD more than and equal to 6 cycles) was observed in 12 of 56 patients with glioma (21.4%). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | LY2157299 was safe, with no cardiac adverse events. |
| Conclusions: | On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mgday is safe for future clinical investigation. |