2. Academic Validation
  3. ANG1005, a Brain-Penetrating Peptide-Drug Conjugate, Shows Activity in Patients with Breast Cancer with Leptomeningeal Carcinomatosis and Recurrent Brain Metastases

ANG1005, a Brain-Penetrating Peptide-Drug Conjugate, Shows Activity in Patients with Breast Cancer with Leptomeningeal Carcinomatosis and Recurrent Brain Metastases

  • Clin Cancer Res. 2020 Jun 15;26(12):2789-2799. doi: 10.1158/1078-0432.CCR-19-3258.
Priya Kumthekar 1,  Shou-Ching Tang 2,  Andrew J Brenner 3,  Santosh Kesari 4,  David E Piccioni 5,  Carey Anders 6,  Jose Carrillo 7,  Pavani Chalasani 8,  Peter Kabos 9,  Shannon Puhalla 10,  Katherine Tkaczuk 11,  Agustin A Garcia 12,  Manmeet S Ahluwalia 13,  Jeffrey S Wefel 14,  Nehal Lakhani 15,  Nuhad Ibrahim 16
Affiliations

Affiliations

  • 1 Northwestern University Feinberg School of Medicine, Chicago, Illinois. [email protected].
  • 2 Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, Mississippi.
  • 3 Mays Cancer Center, UT Health San Antonio, San Antonio, Texas.
  • 4 John Wayne Cancer Institute and Pacific Neuroscience Institute, Santa Monica, California.
  • 5 Department of Neurosciences, UC San Diego Moores Cancer Center, La Jolla, California.
  • 6 Duke Cancer Institute, Durham, North Carolina.
  • 7 John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, California.
  • 8 University of Arizona Cancer Center, Tucson, Arizona.
  • 9 University of Colorado, Anschutz Medical Campus, Greenwood Village, Colorado.
  • 10 University of Pittsburgh Magee Women's Cancer Program, Pittsburgh, Pennsylvania.
  • 11 University Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland.
  • 12 Louisiana State University, New Orleans, Louisiana.
  • 13 Miller Family Endowed Chair in NeuroOncology; Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio.
  • 14 Departments of Neuro-Oncology and Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 15 Cancer and Hematology Centers of Western Michigan, Grand Rapids, Michigan.
  • 16 Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center; Houston, Texas.
PMID: 31969331 DOI: 10.1158/1078-0432.CCR-19-3258
Abstract

Purpose: ANG1005, a novel taxane derivative, consists of three paclitaxel molecules covalently linked to Angiopep-2, designed to cross the blood-brain and blood-cerebrospinal barriers and to penetrate malignant cells via LRP1 transport system. Preclinical and clinical evidence of efficacy with ANG1005 has been previously shown.

Patients and methods: A multicenter, open-label phase II study in adult patients with measurable recurrent brain metastases from breast Cancer (BCBM), with or without leptomeningeal carcinomatosis was conducted (n = 72 BCBM; n = 28 leptomeningeal carcinomatosis subset). ANG1005 was administered intravenously at 600 mg/m2 every 3 weeks. Tumor assessment was based on central nervous system (CNS) RECIST 1.1 for intracranial, and RECIST 1.1 for extracranial response. The primary endpoint was determination of intracranial objective response rate (iORR).

Results: Median age was 47.5 years. Safety profile was similar to that of paclitaxel with myelosuppression as the predominating toxicity. Average number of prior CNS-directed therapies was 2.8 and 94% of the patients had prior taxane treatment. Patient benefit (stable disease or better) was seen in 77% (intracranial) and 86% (extracranial) of the evaluable patients, with iORR of 15% (investigator) or 8% (independent radiology facility [IRF] review). In the leptomeningeal carcinomatosis subset, 79% of the patients had intracranial disease control and estimated median overall survival of 8.0 months (95% CI, 5.4-9.4).

Conclusions: Even though the study preset rule for iORR per IRF was not met in this heavily pretreated population, a notable CNS and systemic treatment effect was seen in all patients including symptom improvement and prolonged overall survival compared to historical control for the subset of patients with leptomeningeal carcinomatosis (n = 28).

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