MD Anderson working on brain-penetration facilitating peptide-paclitaxel conjugate to

[Lani]

target brain mets

Mol Cancer Ther. 2011 Dec 27. [Epub ahead of print]
SAFETY, PHARMACOKINETICS AND ACTIVITY OF GRN1005, A NOVEL CONJUGATE OF ANGIOPEP-2, A PEPTIDE FACILITATING BRAIN PENETRATION, AND PACLITAXEL, IN PATIENTS WITH ADVANCED SOLID TUMORS.
Kurzrock R, Gabrail NY, Chandhasin C, Moulder SL, Smith C, Brenner AJ, Sankhala K, Mita AC, Elian K, Bouchard DC, Sarantopoulos J.
Source
1Investigational Cancer Therapeutics, MD Anderson Cancer Center.
Abstract
GRN1005 is a novel peptide-drug conjugate (PDC) comprised of paclitaxel covalently linked to a peptide, Angiopep-2, that targets the low-density lipoprotein receptor-related protein 1 (LRP-1). This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK) and efficacy of GRN1005 in patients with advanced solid tumors.Patients in sequential cohorts (one patient per cohort until Grade 2 toxicity, then 3 + 3 design) received intravenous GRN1005 at escalating doses between 30 mg/m2 and 700 mg/m2 once every 21 days. In the maximum tolerated dose (MTD) expansion group, patients were required to have brain metastases.Fifty-six patients received GRN1005, including 41 with brain metastases (median number of prior therapies = 4). MTD was 650 mg/m2; the main dose-limiting toxicity was myelosuppression. Sixteen of 20 patients dosed at the MTD had brain metastases. PK was dose-linear and the mean terminal-phase elimination half-life was 3.6 hours. No evidence of accumulation was observed after repeat dosing. No anti-GRN1005 antibodies were detected. Five of the 20 patients (25%) dosed at 650 mg/m2 (MTD), three of whom had previous taxane therapy, achieved an overall partial response (breast, n=2; non-small cell lung cancer, n=2; and ovarian cancer, n=1); responses in all five patients were also accompanied by shrinkage of brain lesions (-17% to -50%). In addition, six patients (11%; doses 30-700 mg/m2) experienced stable disease that lasted > 4 months. GRN1005 was well tolerated and showed activity in heavily-pretreated patients with advanced solid tumors, including those who had brain metastases and/or failed prior taxane therapy.
PMID: 22203732 [

[GracePang]

Thank you, Lani,
for the news. Is there anyone on this board involves in this Phase 2 trial?
Grace