324O - ANG1005, a novel peptide-paclitaxel conjugate crosses the BBB and shows activity in patients with recurrent CNS metastasis from breast cancer, resu...

Date 07 October 2016
Event ESMO 2016 Congress
Session CNS tumours
Topics Central Nervous System Malignancies
Presenter Shou-Ching Tang
Citation Annals of Oncology (2016) 27 (6): 103-113. 10.1093/annonc/mdw367
Authors S. Tang1, P. Kumthekar2, A.J. Brenner3, S. Kesari4, D. Piccioni5, C.K. Anders6, J.A. Carillo7, P. Chalasani8, P. Kabos9, S.L. Puhalla10, A. Garcia11, K. Tkaczuk12, M.S. Ahluwalia13, N. Lakhani14, N. Ibrahim15
  • 1Georgia Regents University Cancer Center, Augusta University, 30912 - Augusta/US
  • 2Neurology, Northwestern University, Chicago/US
  • 3Hematology/oncology, The University of Texas Health Science Center at San Antonio, San Antonio/US
  • 4Neuro-oncology, John Wayne Cancer Institute, Santa Monica/US
  • 5Moores Cancer Center, University of California in San Diego, San Diego/US
  • 6Division Of Hematology Oncology, University of North Carolina - Chapel Hill, Chapel Hill/US
  • 7Neuro-oncology, UC Irvine School of Medicine, Orange/US
  • 8Uacc North Campus Clinic, University of Arizona Cancer Center, Tucson/US
  • 9University Of Colorado Cancer Center, University of Colorado Denver, Aurora/US
  • 10Medicine, Magee-Womens Hospital of UPMC, Pittsburgh/US
  • 11Division Of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 12Division Of Medical Oncology, University of Maryland Greenebaum Cancer Center, 21201-1595 - Baltimore/US
  • 13Cleveland Clinic Lerner College Of Medicine, Cleveland Clinic, Cleveland/US
  • 14Clinical Research, START Midwest/Cancer & Hematology Centers of Western Michigan, PC, 49503 - Grand Rapids/US
  • 15Breast Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US



ANG1005 is a novel taxane derivative, consisting of 3 paclitaxel molecules covalently linked to Angiopep-2, a peptide designed to utilize the LRP-1 transport system to cross the BBB/BCB and to penetrate malignant cells. We conducted an open label phase II clinical study to test its activity in metastatic breast cancer (BC) patients with recurrent brain metastasis (BM), including BCBM patients with newly diagnosed leptomeningeal carcinomatosis (LC).


Adult patients with measurable recurrent BM from breast cancer, with or without LC, were enrolled in this multi-center, open-label study (n = 72 safety population; n = 58 efficacy population). ANG1005 was administered IV at 600 mg/m2 q3w. HER2+ patients were allowed to continue trastuzumab +/- pertuzumab. Intracranial (IC) response was assessed by Gd-MRI using CNS RECIST 1.1 and extracranial response was evaluated per RECIST 1.1.


Median age was 47.5 (26-76) years. Safety was similar to that of paclitaxel with myelosuppression as the predominant toxicity. Patients received a median of 6 (1-29) prior therapies for breast cancer, including 84% with prior taxane treatment. As prior therapy for BM, 87% patients had cranial surgery and/or radiation and 19% patients received systemic therapies. After ANG1005 treatment, best IC response in the efficacy population included 8/58 (14%) patients with PRs [3 (5%) confirmed PRs] and 33/58 (57%) with SD. Extracranial tumor responses of 1 (3%) CR, 2 (7%) PRs and 24 (80%) SDs were seen in 30 evaluable patients, including after prior taxane therapy (93%). The 6 month OS was 63.6 % (95% CI: 42.9, 78.5) for patients with LC. Importantly, Kaplan-Meier estimated median OS was 34.6 weeks (95% CI 24.1-40.9) from first ANG1005 treatment for LC patients. CNS clinical symptoms post-ANG1005 were improved, including in LC patients.


ANG1005 is active against previously treated breast cancer metastasis both within and outside the CNS. The clinical benefit has resulted in an estimated median OS of ∼8 months for the patients with LC, exceeding the historical median of ∼4 months following therapy. A randomized study is planned.

Clinical trial identification

NCT02048059 Last updated: November 16, 2015

Legal entity responsible for the study

Angiochem Inc.


Angiochem Inc.


C.K. Anders: Research funding from Novartis, Sanofi, toBBB, Geron, Angiochem, Merrimack, PUMA, Lilly, Merck, Oncothyreon. Uncompensated advisory role with Novartis, Sanofi, toBBB, Geron, Angiochem, Merrimack, Lilly, Genentech, Nektar, Kadmon.

All other authors have declared no conflicts of interest.