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ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases.

Abstract

PURPOSE

ANG1005, a novel taxane derivative, consists of 3 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.

EXPERIMENTAL DESIGN

A multi-center, open-label phase 2 study in adult patients with measurable recurrent brain metastases from breast cancer (BCBM), with or without leptomeningeal carcinomatosis (LC) was conducted (n=72 BCBM; n=28 LC subset). ANG1005 was administered IV at 600 mg/m2 q3w. Tumor assessment was based on 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 2.6 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 review). In the LC 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 pre-set 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, particularly in LC patients, including symptom improvement and prolonged overall survival compared to historical control.

Authors+Show Affiliations

Department of Neurology, Northwestern University Feinberg School of Medicine Priya.Kumthekar@nm.org.Cancer Institute, University of Mississippi Medical Center.Department of Hematology and Oncology, The University of Texas Health Science Center at San Antonio.Department of Neurosciences and Neurotherapeutics, John Wayne Cancer Institute.Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center.Medical Oncology, Duke Cancer Institute.Department of Neurosciences and Neurotherapeutics, John Wayne Cancer Institute.University of Arizona Cancer Center.Medical Oncology, University of Colorado School of Medicine.Medicine, University of Pittsburgh School of Medicine.Breast Evaluation & Treatment Program, University of Maryland Greenebaum Comprehensive Cancer Center.Medicine, Louisiana State University.Oncology, Cleveland Clinic.Neuro-Oncology, The University of Texas MD Anderson Cancer Center.START Midwest, Cancer and Hematology Centers of Western Michigan.Breast Medical Oncology, University of Texas MD Anderson Cancer Center.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31969331

Citation

Kumthekar, Priya, et al. "ANG1005, a Brain Penetrating Peptide-drug Conjugate, Shows Activity in Patients With Breast Cancer With Leptomeningeal Carcinomatosis and Recurrent Brain Metastases." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 2020.
Kumthekar P, Tang SC, Brenner AJ, et al. 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.
Kumthekar, P., Tang, S. C., Brenner, A. J., Kesari, S., Piccioni, D. E., Anders, C. K., ... Ibrahim, N. K. (2020). ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, doi:10.1158/1078-0432.CCR-19-3258.
Kumthekar P, et al. 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 Jan 22; PubMed PMID: 31969331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases. AU - Kumthekar,Priya, AU - Tang,Shou-Ching, AU - Brenner,Andrew J, AU - Kesari,Santosh, AU - Piccioni,David E, AU - Anders,Carey K, AU - Carrillo,Jose A, AU - Chalasani,Pavani, AU - Kabos,Peter, AU - Puhalla,Shannon L, AU - Tkaczuk,Katherine H R, AU - Garcia,Agustin, AU - Ahluwalia,Manmeet S, AU - Wefel,Jeffrey S, AU - Lakhani,Nehal, AU - Ibrahim,Nuhad K, Y1 - 2020/01/22/ PY - 2020/01/17/accepted PY - 2019/10/07/received PY - 2019/12/12/revised PY - 2020/1/24/entrez JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. N2 - PURPOSE: ANG1005, a novel taxane derivative, consists of 3 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. EXPERIMENTAL DESIGN: A multi-center, open-label phase 2 study in adult patients with measurable recurrent brain metastases from breast cancer (BCBM), with or without leptomeningeal carcinomatosis (LC) was conducted (n=72 BCBM; n=28 LC subset). ANG1005 was administered IV at 600 mg/m2 q3w. Tumor assessment was based on 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 2.6 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 review). In the LC 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 pre-set 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, particularly in LC patients, including symptom improvement and prolonged overall survival compared to historical control. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/31969331/ANG1005,_a_brain_penetrating_peptide-drug_conjugate,_shows_activity_in_patients_with_breast_cancer_with_leptomeningeal_carcinomatosis_and_recurrent_brain_metastases L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=31969331 DB - PRIME DP - Unbound Medicine ER -