paclitaxel trevatide (ANG1005) / Angiochem - LARVOL DELTA

Phase II trial of blood-brain barrier permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma. (PubMed, Neurooncol Adv) - P2 | "Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). A dose of 600 mg/m2 was determined to be safe in this study. However, the primary efficacy endpoint was not met in the NCT01967810-ANG1005 trial, and no further studies are planned in the glioma setting with this compound."

Journal • P2 data • Alopecia • Brain Cancer • CNS Tumor • Fatigue • Glioblastoma • Glioma • Hematological Disorders • Immunology • Malignant Glioma • Oncology • Solid Tumor

Pharmacotherapy for leptomeningeal disease in breast cancer. (PubMed, Cancer Treat Rev) - "Systemic therapies under investigation for LMD in breast cancer include tucatinib, trastuzumab deruxtecan, and paclitaxel trevatide; trastuzumab is the main intrathecal agent currently under investigation. Large retrospective cohorts with various inclusion criteria and treatment regimens provide some real-world data. However, there remains an urgent need for randomised clinical trials which include patients with LMD across all breast cancer subtypes."

Journal • Review • Brain Cancer • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Angiochem Inc | Trial primary completion date: Mar 2024 ➔ Dec 2024

Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

Systemic therapy for breast cancer brain metastases (SABCS 2019) - P2; "For patients with HER2-positive breast cancer, the combination of lapatinib and capecitabine has been associated with CNS response rates of 66% in the upfront setting, and 18-38% in patients whose disease has progressed after prior radiotherapy...The TBCRC 022 trial is now enrolling to a cohort who will receive ado-trastuzumab emtansine + neratinib...Notably, patients with brain metastases (either stable or progressive) are allowed on the current tucatinib registration trial (HER2CLIMB; NCT02614794). Finally, there is evidence that monoclonal antibodies and antibody drug conjugates may have CNS activity; for example, trastuzumab-emtansine has been reported to lead to CNS regressions in up to 40% of patients, based upon case series from several institutions, and in preliminary data from the PATRICIA study, the regimen of high dose trastuzumab (6 mg/kg weekly) plus pertuzumab was associated with CNS responses and prolonged stable disease in a subset of patients...Results..."

Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Angiochem Inc | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Angiochem Inc | Trial completion date: Mar 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

ANG1005 in leptomeningeal disease (ANGLeD) trial: A randomized, open-label, phase 3 study of ANG1005 compared with Physician's Best Choice in HER2-negative breast cancer patients with newly diagnosed leptomeningeal carcinomatosis and previously treated brain metastases (SABCS 2018) - "...ANG1005 is a novel peptide-drug conjugate, consisting of 3 paclitaxel molecules covalently linked to a peptide that targets the LRP-1 receptor to cross both BCB and BBB, and enter the tumor cells, where the paclitaxel is cleaved off to exert its anti-tumor activity...Allowed PBC therapies include capecitabine, eribulin, or high-dose IV methotrexate...Interim analysis for OS (using O'Brien Fleming boundaries for efficacy and a fixed HR=1 for futility) will be performed when a total of 55 death events are reached across both arms.Study Accrual: Target accrual is 150 patients. The study is currently planned to start in the fall of 2018. "

Clinical • P3 data • Brain Cancer • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Dec 2023 ➔ Mar 2024; Trial primary completion date: Mar 2023 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Sep 2023 ➔ Dec 2023; Trial primary completion date: Dec 2022 ➔ Mar 2023

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: May 2023 ➔ Sep 2023; Trial primary completion date: Aug 2022 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

ANG1005 in Patients With Recurrent High-Grade Glioma (clinicaltrials.gov) - P2; N=83; Active, not recruiting; Sponsor: Angiochem Inc; Trial primary completion date: Jul 2017 ➔ Dec 2017

Trial primary completion date • Biosimilar • Solid Tumor

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Dec 2022 ➔ Mar 2023; Trial primary completion date: Mar 2022 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

GRN1005 alone or in combination with trastuzumab in breast cancer patients with brain metastases (GRABM-B) (clinicaltrials.gov) - P2, N=100; Recruiting; Clinical Protocol: Study drug dose: 650mg/m2-> 550mg/m2

Clinical protocol • Oncology

A phase 2, multi-center, open label study evaluating the efficacy and safety of GRN1005 alone or in combination with trastuzumab in patients with brain metastases from breast cancer (SABCS 2012) - P2, N=24; Study ID: CP1005B016; “...Six (25%) pts have discontinued treatment with GRN1005, including 2 due to iPD and 2 due to adverse events (AE). One additional pt had clinical progression and discontinued GRN1005. The AEs observed at 650 mg/m2 are qualitatively consistent with conventional paclitaxel but are more frequent and more severe than observed with q3 week paclitaxel which led to a protocol amendment and dose reduction to 550 mg/m2 for all subsequent pts...”

P2 data • Breast Cancer • Oncology

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Jul 2022 ➔ Dec 2022; Trial primary completion date: Oct 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • HER-2

ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases. (PubMed, Clin Cancer Res) - "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."

Clinical • Journal

Nanotechnology, in silico and endocrine-based strategy for delivering paclitaxel and miRNA: Prospects for the therapeutic management of breast cancer. (PubMed, Semin Cancer Biol) - "miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed...An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2...miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers."

IO Biomarker • Journal • Review • BCL2

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Mar 2022 ➔ Jul 2022; Trial primary completion date: Jun 2021 ➔ Oct 2021

Clinical • Trial completion date • Trial primary completion date

DISRUPTING THE BLOOD-BRAIN BARRIER IN NEURO-ONCOLOGY: INNOVATIONS, ACHIEVEMENTS, AND LESSONS LEARNED FROM CLINICAL TRIALS (SNO 2019) - "Mannitol was the most common drug-based method (16/33, 5 Phase II), followed by RMP-7 (8/33, 3 Phase II), Ang1005 (7/33, 4 Phase II and one pending Phase III), and Regadenoson (2/33, one Phase 0 and one Phase I). Objective establishment of BBB disruption was limited. Concerted and standardized clinical trial efforts are needed."

Clinical

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Dec 2021 ➔ Mar 2022; Initiation date: Sep 2019 ➔ Dec 2019; Trial primary completion date: Mar 2021 ➔ Jun 2021

Clinical • Trial completion date • Trial initiation date • Trial primary completion date

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: May 2021 ➔ Dec 2021; Initiation date: Apr 2019 ➔ Sep 2019

Clinical • Trial completion date • Trial initiation date

ANGLeD: ANG1005 in Leptomeningeal Disease From Breast Cancer (clinicaltrials.gov) - P3; N=150; Not yet recruiting; Sponsor: Angiochem Inc; Trial completion date: Jan 2021 ➔ May 2021; Initiation date: Dec 2018 ➔ Apr 2019; Trial primary completion date: Dec 2020 ➔ Apr 2021

Clinical • Trial completion date • Trial initiation date • Trial primary completion date