Delving into the Latest Updates on DI-Leu16-IL2 with Synapse

Overview

Basic Info

Drug Type

Antibody fusion proteins

Synonyms

Anti-CD20 monoclonal antibody-interleukin-2 fusion protein, DI-Leu16-IL2 immunocytokine, de-immunized anti-CD20-IL-2 immunocytokine DI-Leu16-IL-2

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Target

CD20 x IL-2R

Action

inhibitors, agonists

Mechanism

CD20 inhibitors(B-lymphocyte antigen CD20 inhibitors), IL-2R agonists(Interleukin-2 receptor agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

Non-Hodgkin LymphomaLymphoma

Inactive Indication

B-Cell Lymphoma

Originator Organization

Merck Serono SA

Active Organization

City of Hope National Medical CenterEMD Lexigen Research Center Corp.Merck Serono SA

+ [1]

Inactive Organization

Alopexx Oncology, LLC

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 16279555VH

Sequence Code 14671992VL

This is an open-label extension study enrolling participants experiencing clinical benefit following 6 cycles of DI-Leu16-IL2 while enrolled in the Alopexx Oncology Dose-Escalation AO-101 study (NCT01874288). Participants will be permitted to continue to receive DI-Leu16-IL2 at the same dose, schedule, and route of administration they received during Study AO-101 (Main Study). Prior pre-treatment (for example, Rituximab) will continue as before.

Start Date04 Nov 2014

Sponsor / Collaborator

Alopexx Oncology, LLC

NCT01874288

/ TerminatedPhase 1/2

A Phase I/II Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered Subcutaneously in Patients With B-cell Non-Hodgkin Lymphoma (NHL)

This dose-escalation study is designed for determining the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to participants with cluster of differentiation 20 (CD20) positive NHL that have failed standard rituximab-containing therapy.

Start Date25 Nov 2013

Sponsor / Collaborator

Alopexx Oncology, LLC

NCT00720135

/ CompletedPhase 1IIT

A Phase I Study of De-Immunized DI-Leu16-IL2 Immunocytokine in Patients With B-Cell Non-Hodgkin Lymphoma

RATIONALE: Biological therapies, such as fusion protein cytokine therapy, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fusion protein cytokine therapy together with rituximab may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of fusion protein cytokine therapy when given after rituximab in treating patients with B-cell non-Hodgkin lymphoma.

Start Date01 Jan 2008

Sponsor / Collaborator

City of Hope National Medical Center

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100 Clinical Results associated with DI-Leu16-IL2

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100 Translational Medicine associated with DI-Leu16-IL2

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100 Patents (Medical) associated with DI-Leu16-IL2

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1

Literatures (Medical) associated with DI-Leu16-IL2

15 May 2005·BloodQ1 · MEDICINE

An anti-CD20–IL-2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma

Q1 · MEDICINE

Article

Author: Williams, Steven ; Carr, Frank ; Forman, Stephen ; Lan, Yan ; Raubitschek, Andrew ; Gillies, Stephen D. ; Lo, Kin-Ming

AbstractWe have engineered an anti-CD20–interleukin 2 (IL-2) immunocytokine (ICK) based on the Leu16 anti-CD20 antibody and have deimmunized both the variable (V) regions as well as the junction between the heavy (H) chain constant region and IL-2. Mutations were made to remove potential T-cell epitopes identified by in silico binding to major histocompatibility complex (MHC) class II molecules. The resulting immunocytokine, DI-Leu16-IL-2, retained full anti-CD20 activity as assessed by fluorescence-activated cell-sorting (FACS) analysis, and had enhanced antibody-dependent cellular cytotoxicity (ADCC) effector function relative to the DI-Leu16 antibody or control anti-CD20 antibody (rituximab). In a severe combined immunodeficient (SCID) mouse model of disseminated, residual lymphoma, anti-CD20–IL-2 immunocytokines based on Leu16 were far more effective at a dose of 0.25 mg/kg than anti-CD20 antibody given at 25/mg/kg, despite a shorter half-life of the ICK. Anti-CD20–IL-2 was also far more effective than a control ICK targeted to an antigen with greatly reduced expression on Daudi tumor cells, or various combinations of anti-CD20 antibodies and IL-2. Antitumor activity of DI-Leu16-IL-2 was shown to partially but not entirely depend on Fc receptor (R) binding, suggesting that ADCC and targeting of IL-2 both play roles in the mechanism of tumor clearance. Based on these animal models, DI-Leu16-IL-2 could offer therapeutic potential for patients with CD20 positive lymphoma. Clinical trials are currently under development.

100 Deals associated with DI-Leu16-IL2

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
B-Cell Lymphoma	Phase 2	United States	Alopexx Oncology, LLC	25 Nov 2013
Non-Hodgkin Lymphoma	Phase 2	-	Merck Serono SA	-
Non-Hodgkin Lymphoma	Phase 2	-	Provenance Biopharmaceuticals Corp.	-
Lymphoma	Preclinical	United States	City of Hope National Medical Center	16 Nov 2004
Lymphoma	Preclinical	United States	EMD Lexigen Research Center Corp.	16 Nov 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02151903 (CTgov)	Phase 1/2	B-Cell Lymphoma	5	DI-Leu16-IL2 (DI-Leu16-IL2 1.0 mg/m^2)	(pojjgsjvsk) = huihhctmbn utljfkpjlg (cxnjulncst, nqzyoloqmb - xwcqopklsf) View more	-	27 Nov 2020
				DI-Leu16-IL2 (DI-Leu16-IL2 2.0 mg/m^2)	(pojjgsjvsk) = dtaditvrxl utljfkpjlg (cxnjulncst, ojynhgkrmj - oodgemoofb) View more
NCT01874288 (DI-Leu16-IL2, CTgov)	Phase 1/2	B-Cell Lymphoma	24	DI-Leu16-IL2 (DI-Leu16-IL2 0.5 mg/m^2)	jukavjnexx(yzvkkwlmvz) = pntkqrahwq mognqwycew (hhmtetikno, bdcfpxhpcg - wozpvzylje) View more	-	24 Nov 2020
				DI-Leu16-IL2 (DI-Leu16-IL2 1.0 mg/m^2)	jukavjnexx(yzvkkwlmvz) = ecjrgcbsrs mognqwycew (hhmtetikno, taxamiivim - jffdzpyboh) View more
NCT01874288 (ASCO2016)	Phase 1/2	B-cell lymphoma recurrent	18	DI-Leu16-IL2	bsewwnwbnm(ldwqfrvbct) = DLT occurred in 2 pts at 6 mg/m2 with delayed (8-10 days) grade 3 cytokine release syndrome, suggesting effector cell expansion as the cause. ctlmhyvmts (womrhrdjes ) View more	Positive	20 May 2016

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Biosimilar

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