| General information |
| Database: | DB00133 |
| Objective: | Inhibition of TGFbeta RImediated signaling pathways blocks tumor growth and metastases in nonclinical studies. Galunisertib (LY2157299) had antitumor effects with acceptable safety/tolerability in a firstinhuman dose (FHD) study conducted mainly in Caucasian patients with glioma. In this study, they assessed safety/tolerability, pharmacokinetics (PK), and tumor response in Japanese patients. |
| Authors: | Fujiwara Y |
| Title: | Phase 1 study of galunisertib, a TGFbeta receptor I kinase inhibitor, in Japanese patients with advanced solid tumors. |
| Journal: | Cancer Chemother Pharmacol. |
| Year: | 2015 |
| PMID: | 26526984 |
| Trial Design |
| Clinical Trial Id: | NCT01722825 |
| Agent: | galunisertib
|
| Target: | TGFbeta receptor type I
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced and/or metastatic disease refractory, most common types of cancer were pancreatic (n = 5) and lung cancer (n = 3). |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a nonrandomized, openlabel, doseescalationphase I study |
| Key Patients Feature: | Patients with advanced and/or metastatic disease refractory |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were assigned sequentially to Cohort1 (80 mg) or Cohort2 (150 mg) of galunisertib, administered twice daily and treated using 2week on, 2week off treatment cycles. Dose escalation was guided by predefined PK criteria and doselimiting toxicities (DLT). |
| Primary End Point: | safety/tolerability, pharmacokinetics, and tumor response |
| Secondary End Point: | NA |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | Maximum plasma concentration was reached within 2 h postdose, and the mean elimination halflife was 9 h. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | 7 patients (Cohort1, n = 2; Cohort2, n = 5) experienced possibly galunisertibrelated TEAEs( treatmentemergent adverse events). The most frequent related TEAEs were brain natriuretic peptide increased (n = 2), leukopenia (n = 2), and rash (n = 2). No cardiovascular toxicities or other DLTs were reported. PK profile of galunisertib was consistent with the FHD study. |
| Conclusions: | Galunisertib had an acceptable tolerability and safety profile in Japanese patients with advanced cancers. |