| General information |
| Database: | DB00591 |
| Objective: | GRN1005 is a peptidedrug conjugate with the ability to penetrate the bloodbrain barrier (BBB) and tumor cells by targeting the lowdensity lipoprotein receptorrelated protein1. they conducted a firstinhumanphase I trial of GRN1005 in patients with recurrent glioma. |
| Authors: | Drappatz J, et al |
| Title: | Phase I study of GRN1005 in recurrent malignant glioma. |
| Journal: | Clin Cancer Res |
| Year: | 2013 |
| PMID: | 23349317 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | GRN1005
|
| Target: | lipoprotein receptorrelated protein1
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | malignant glioma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I Study |
| Key Patients Feature: | Eligibility included histologically confirmed WorldHealth Organization (WHO) grades 2 to 4 glioma withunequivocal radiographic progression, informed consent, age 18 years, measurable disease, Eastern CooperativeOncology Group (ECOG) performance status score 2;MRI 21 days of registration on a stable steroid dose; lifeexpectancy 3 months; adequate bone marrow function(neutrophils 1, 500/mL; platelets 100, 000/mL), adequate hepatic and renal function [alanine aminotransferase(ALT)/alkaline phosphatase < 2.5 normal; bilirubin < 1.5 normal, creatinine clearance > 60 mL/min]; 2 weeksfrom cytochrome P450 enzyme-inducing antiepilepticdrugs (EIAED), 28 days from cytotoxic or investigationalagents; and 6 weeks from bevacizumab |
| Biomarker: | LRP1 expression |
| Biomark Analysis: | LPR1 levels were variable anddid not correlate with drug concentration at resection. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received GRN1005 by intravenous infusion every 3 weeks. Doses were escalated using a modified Fibonacci scheme. |
| Primary End Point: | MTD |
| Secondary End Point: | pharmacokinetics (PK),immunogenicity, and preliminary efficacy |
| Patients Number: | 63 |
| Trial Results |
| DLT_MTD: | The MTD was 650 mg/m(2) every 3 weeks. Doselimiting toxicities were grade 3 mucositis and grade 4 neutropenia. |
| Objective Response Rate: | Eight of 27 patients dosed more than and equal to 420 mg/m(2) had stable disease, which lasted a median of 51 days. |
| 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): | Therapy was well tolerated with neutropenia, leucopenia, and fatigue as the most frequent drugassociated grade 3/4 or higher toxicities. |
| Conclusions: | GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommendedphase II dose is 650 mg/m(2) every 3 weeks. |