| General information |
| Database: | DB00137 |
| Objective: | Golvatinib showed preclinical evidence of antitumor activity. This phase 1 study was performed to determine the MTD, safety, PK, PD and preliminary activity of golvatinib |
| Authors: | Gennaro Daniele, et al |
| Title: | NA |
| Journal: | J Clin Oncol |
| Year: | 2012 ASCO Annual Meeting |
| PMID: | J Clin Oncol 30, 2012 (suppl; abstr 3030) |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | golvatinib
|
| Target: | cMet and Eph receptor
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I dosefinding study |
| Key Patients Feature: | Patients (pts) with advanced solid tumors, ECOG PS 01, more than and equal to 18 years (yrs) and adequate organ function were eligible. (M/F: 21/13; median age 63.5yrs [range 3278]); Tumor types were colorectal (n=15), lung (n=4), renal (n=4), esophageal (n=2), melanoma (n=2) and others (n=7). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Golvatinib was administered orally, once daily (QD), continuously. Blood samples for PK and PD analysis were collected at multiple timepoints. Mandatory tumor biopsies for PD analysis were taken pre and post Cycle 1 in an expanded MTD cohort. Pts were treated at 6 dose levels: 100, 200, 270, 360, 450 and 400 mg |
| Primary End Point: | MTD, safety, PK, PD and preliminary activity |
| Secondary End Point: | NA |
| Patients Number: | 34 |
| Trial Results |
| DLT_MTD: | Three DLTs were observed: Gr3 GGT and alkaline phosphatase (n=1; 200mg) and repeated Gr2 (n=1) and Gr3 (n=1) fatigue, both at 450mg. The MTD was determined to be 400 mg QD. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Best response was stable disease in 6 pts lasting >84 days.Tumor PD analysis in 5 pts at 400 mg demonstrated a baseline elevated MET gene copy number, with cMet overexpression and post treatment decline in phospho(p)cMet expression in 1 pt; posttreatment decline in pcMet in a 2nd pt, and posttreatment decline in pERK in a 3rd pt. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Frequently occurring adverse events ([AEs]; all grades) were fatigue: 68% (Gr3: 15%), diarrhea: 65%, nausea: 62%, vomiting: 53%, decreased appetite: 47% (Gr3: 9%), ALT increase: 38% and AST increase: 23%. No Gr4 AEs were observed. |
| Conclusions: | Golvatinib at an MTD of 400 mg QD has manageable toxicity. Preliminary PD analysis demonstrated evidence of cMet target modulation. Further evaluation will continue inphase 2 combination studies. |