Delving into the Latest Updates on At 211 MAb BC8-B10 with Synapse

Overview

Basic Info

Drug Type

Radiolabeled antibody, Therapeutic radiopharmaceuticals

Synonyms

211At-BC8-B10

Target

CD45

Action

inhibitors

Mechanism

CD45 inhibitors(Leukocyte common antigen inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

NeoplasmsAcute lymphoblastic leukemia recurrentChronic Myelomonocytic Leukemia+ [8]

Inactive Indication-

Originator Organization

Fred Hutchinson Cancer Research Center

Active Organization

National Cancer Institute

Fred Hutchinson Cancer Center

Fred Hutchinson Cancer Research Center

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Boost your research with our ADC technology data.

login

or

view full example data

Boost your research with our ADC technology data.

This phase I/II trial studies the best dose of total body irradiation with astatine-211 BC8-B10 monoclonal antibody for the treatment of patients with nonmalignant diseases undergoing hematopoietic cell transplant. Radiation therapy uses high energy gamma rays to kill cancer cells and shrink tumors. Astatine-211-labeled BC8-B10 monoclonal antibody is a monoclonal antibody, called anti-CD45 monoclonal antibody BC8-B10, linked to a radioactive/toxic agent called astatine 211. Anti-CD45 monoclonal antibody BC8-B10 is attached to CD45 antigen positive cancer cells in a targeted way and delivers astatine 211 to kill them. Giving astatine-211 BC8-B10 monoclonal antibody and total-body irradiation before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells.

Start Date16 Jun 2020

Sponsor / Collaborator

Fred Hutchinson Cancer Research Center

[+1]

NCT03670966

/ RecruitingPhase 1/2IIT

A Phase I/II Study Evaluating Escalating Doses of 211At-Labeled Anti-CD45 MAb BC8-B10 (211At-BC8-B10) Followed by Related Haplo-Identical Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Leukemia or Myelodysplastic Syndrome (MDS)

This phase I/II trial studies the side effects and best dose of a radioactive agent linked to an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after a transplant may stop this from happening.

Start Date10 Jul 2019

Sponsor / Collaborator

Fred Hutchinson Cancer Research Center

[+1]

100 Clinical Results associated with At 211 MAb BC8-B10

Login to view more data

100 Translational Medicine associated with At 211 MAb BC8-B10

Login to view more data

100 Patents (Medical) associated with At 211 MAb BC8-B10

Login to view more data

2

Literatures (Medical) associated with At 211 MAb BC8-B10

01 May 2017·Nuclear Medicine and BiologyQ4 · MEDICINE

Development of a preclinical 211 Rn/ 211 At generator system for targeted alpha therapy research with 211 At

Q4 · MEDICINE

Article

Author: Wilbur, D Scott ; Ruth, Thomas J ; Crawford, Jason R ; Schaffer, Paul ; Yang, Hua ; Kunz, Peter

INTRODUCTIONThe availability of ²¹¹At for targeted alpha therapy research can be increased by the ²¹¹Rn/²¹¹At generator system, whereby ²¹¹At is produced by ²¹¹Rn electron capture decay. This study demonstrated the feasibility of using generator-produced ²¹¹At to label monoclonal antibody (BC8, anti-human CD45) for preclinical use, following isolation from the ²⁰⁷Po contamination also produced by these generators (by ²¹¹Rn α-decay).METHODS²¹¹Rn was produced by ²¹¹Fr electron capture decay following mass separated ion beam implantation and chemically isolated in liquid alkane hydrocarbon (dodecane). ²¹¹At produced by the resulting ²¹¹Rn source was extracted in strong base (2N NaOH) and purified by granular Te columns. BC8-B10 (antibody conjugated with closo-decaborate(2-)) was labeled with generator-produced ²¹¹At and purified by PD-10 columns.RESULTSAqueous solutions extracted from the generator were found to contain ²¹¹At and ²⁰⁷Po, isolated from ²¹¹Rn. High radionuclidic purity was obtained for ²¹¹At eluted from Te columns, from which BC8-B10 monoclonal antibody was successfully labeled. If not removed, ²⁰⁷Po was found to significantly contaminate the final ²¹¹At-BC8-B10 product. High yield efficiencies (decay-corrected, n=3) were achieved for ²¹¹At extraction from the generator (86%±7%), Te column purification (70%±10%), and antibody labeling (76%±2%).CONCLUSIONSThe experimental ²¹¹Rn/²¹¹At generator was shown to be well-suited for preclinical ²¹¹At-based research.ADVANCES IN KNOWLEDGEWe believe that these experiments have furthered the knowledge-base for expanding accessibility to ²¹¹At using the ²¹¹Rn/²¹¹At generator system.IMPLICATIONS FOR PATIENT CAREAs established by this work, the ²¹¹Rn/²¹¹At generator has the capability of facilitating preclinical evaluations of ²¹¹At-based therapies.

PLOS ONEQ3 · CROSS-FIELD

cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies

Q3 · CROSS-FIELD

ArticleOA

Author: Green, Damian J ; Wilbur, D Scott ; Storb, Rainer ; Manger, Ronald L ; Press, Oliver W ; Dorman, Eric F ; Chyan, Ming-Kuan ; Kenoyer, Aimee L ; Woodle, Douglas R ; Wong, Roger ; Nartea, Margaret ; Hamlin, Donald K ; Orozco, Johnnie J ; Li, Yawen ; Emery, Robert C ; Sandmaier, Brenda M

The objective of this study was to translate reaction conditions and quality control methods used for production of an astatine-211(211At)-labeled anti-CD45 monoclonal antibody (MAb) conjugate, 211At-BC8-B10, from the laboratory setting to cGMP production. Five separate materials were produced in the preparation of 211At-BC8-B10: (1) p-isothiocyanato-phenethyl-closo-decaborate(2-) (B10-NCS), (2) anti-CD45 MAb, BC8, (3) BC8-B10 MAb conjugate, (4) [211At]NaAt, and (5) 211At-BC8-B10. The 211At-labeling reagent, B10-NCS, was synthesized as previously reported. BC8 was produced, then conjugated with B10-NCS under cGMP conditions to form BC8-B10. [211At]NaAt was produced by α-irradiation of Bi targets, followed by isolation of the 211At using a "wet chemistry" method. The clinical product, 211At-BC8-B10, was prepared by reacting [211At]NaAt with BC8-B10 in NH4OAc buffer (pH 5.5) for 2 min at room temperature, followed by size-exclusion chromatography purification. Quality control tests conducted on the 211At-BC8-B10 included evaluations for purity and identity, as well as pyrogen and sterility tests. Stability of the 211At-BC8-B10 in 25 mg/mL sodium ascorbate solution was evaluated at 1, 2, 4, 6 and 21 h post isolation. For qualification, three consecutive 211At-BC8-B10 clinical preparations were successfully conducted in the cGMP suite, and an additional cGMP clinical preparation was carried out to validate each step required to deliver 211At-BC8-B10 to a patient. These cGMP preparations provided 0.80-1.28 Gbq (21.5-34.5 mCi) of 211At-BC8-B10 with radiochemical purity of >97%. The preparations were found to be sterile and have a pyrogen level <0.50 EU/mL. Cell binding was retained by the 211At-BC8-B10. 211At-BC8-B10 in ascorbic acid solution demonstrated a radiochemical stability of >95% for up to 21 h at room temperature. The experiments conducted have defined conditions for translation of 211At-BC8-B10 production from the laboratory to cGMP suite. This study has allowed the initiation of a phase I/II clinical trial using 211At-BC8-B10 (NCT03128034).

100 Deals associated with At 211 MAb BC8-B10

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute lymphoblastic leukemia recurrent	Phase 2	United States	National Cancer Institute	10 Jul 2019
Chronic Myelomonocytic Leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Myelodysplastic Syndromes	Phase 2	United States	National Cancer Institute	10 Jul 2019
Recurrent Acute Leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Recurrent Mixed Phenotype Acute Leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Refractory acute myeloid leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Refractory Adult Acute Lymphoblastic Leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Refractory Mixed Phenotype Acute Leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Relapsing acute myeloid leukemia	Phase 2	United States	National Cancer Institute	10 Jul 2019
Neoplasms	Phase 2	-	Fred Hutchinson Cancer Research Center	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Login to view more data

Translational Medicine

Boost your research with our translational medicine data.

login

or

view full example data

Boost your research with our translational medicine data.

Deal

Boost your decision using our deal data.

login

or

view full example data

Boost your decision using our deal data.

Core Patent

Boost your research with our Core Patent data.

login

or

view full example data

Boost your research with our Core Patent data.

Clinical Trial

Identify the latest clinical trials across global registries.

login

or

view full example data

Identify the latest clinical trials across global registries.

Approval

Accelerate your research with the latest regulatory approval information.

login

or

view full example data

Accelerate your research with the latest regulatory approval information.

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

login

or

view full example data

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

Understand key drug designations in just a few clicks with Synapse.

login

or

view full example data

Understand key drug designations in just a few clicks with Synapse.


No Data