Delving into the Latest Updates on Tucotuzumab celmoleukin with Synapse

Overview

Basic Info

Drug Type

Antibody

Synonyms

KS-interleukin-2, Tucotuzumab celmoleukin (USAN/INN)

+ [2]

Target

EpCAM x IL-2R

Action

inhibitors, agonists

Mechanism

EpCAM inhibitors(Epithelial cell adhesion molecule inhibitors), IL-2R agonists(Interleukin-2 receptor agonists)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseRespiratory Diseases+ [2]

Active Indication-

Inactive Indication

Bladder CancerColorectal CancerKidney Neoplasms+ [6]

Originator Organization

EMD Lexigen Research Center Corp.

Active Organization-

Inactive Organization

EMD Serono, Inc.Merck KGaAEMD Lexigen Research Center Corp.

+ [1]

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 1191632848H

Source: *****

Sequence Code 88455L

Source: *****

An open-label, randomised, phase II study in subjects with extensive disease, small cell lung cancer (ED-SCLC) after an initial response (complete response or partial response) to platinum-based therapy to determine the effect of EMD 273066 following low-dose cyclophosphamide on disease progression and survival versus best supportive care alone.

Start Date26 Mar 2008

Sponsor / Collaborator

Merck KGaA

NCT00408967

/ WithdrawnPhase 2

An Open-label Phase II Study of Two Dose Levels of EMD 273066 Administered With Low-dose Cyclophosphamide Following Objective Response to Second-line Chemotherapy in Women With Recurrent Ovarian Carcinoma

The purpose of this study is to determine if either of two doses of EMD 273066 when given with a low dose of cyclophosphamide will result in a second time to progression that is as long or longer than the first time to progression

Start Date31 Dec 2006

Sponsor / Collaborator

EMD Serono, Inc.

NCT00132522

/ CompletedPhase 1

A Study to Find the Highest Dose of Biological Study Drug (EMD 273066) That Can Be Given Safely to Patients With Recurrent EpCAM Positive Ovarian, Prostate, Colorectal or Non-Small Cell Lung Cancers When First Given a Low Dose of Cyclophosphamide

This study is looking at the safety and tolerability of the experimental biological drug EMD 273066 when given with low dose cyclophosphamide to patients with recurring EpCAM positive ovarian, prostate, colorectal or non-small cell lung cancers. EMD 273066 is an experimental biological drug that may increase the immune response to certain cancers. Patients will be enrolled in groups of 3, with each successive group receiving a higher dose if the prior group adequately tolerates the study medication.

Start Date01 May 2005

Sponsor / Collaborator

EMD Serono, Inc.

100 Clinical Results associated with Tucotuzumab celmoleukin

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100 Translational Medicine associated with Tucotuzumab celmoleukin

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100 Patents (Medical) associated with Tucotuzumab celmoleukin

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8

Literatures (Medical) associated with Tucotuzumab celmoleukin

01 Nov 2015·Anti-Cancer DrugsQ4 · MEDICINE

Cyclophosphamide and tucotuzumab (huKS-IL2) following first-line chemotherapy in responding patients with extensive-disease small-cell lung cancer

Q4 · MEDICINE

Article

Author: Krzakowski, Maciej J. ; Komarnitsky, Philip B. ; Serwatowski, Piotr ; Ramlau, Rodryg ; Milanowski, Janusz ; Kramer, Daniel ; Gladkov, Oleg ; Tomeczko, Janusz

The humanized KS-interleukin-2, tucotuzumab (huKS-IL2; EMD 273066), is an EpCAM-specific immunocytokine with reported immunologic activity in combination with cyclophosphamide. This Phase 2, randomized, open-label study compared tucotuzumab/cyclophosphamide, administered as maintenance, with best supportive care (BSC) in patients with extensive-disease small-cell lung cancer (ED-SCLC) who responded to first-line platinum-based chemotherapy with/without prophylactic cranial irradiation (PCI). Patients received cyclophosphamide (300 mg/m, Day 1 of every 3-week cycle), followed by tucotuzumab (1.5 mg/m, Days 2-4) until disease progression. The primary endpoint was 6-month progression-free survival (PFS); the secondary objectives included overall survival (OS), treatment response, and safety. The 6-month PFS rate was lower in the tucotuzumab/cyclophosphamide group (n=64) than in the BSC group (n=44): 6.4 versus 12.2% [hazard ratio (HR): 0.98; 80% confidence interval (CI): 0.74-1.31]. HRs for PFS, time to progression, and OS indicated a similar risk of disease progression and death in both groups and best overall responses were generally comparable. For patients with previous PCI (n=26), there was a nonsignificant trend toward prolonged median PFS (1.7 vs. 1.5 months; HR: 0.60; 80% CI: 0.33-1.11) and OS (21.5 vs. 14.3 months; HR: 0.58; 80% CI: 0.31-1.05) in the tucotuzumab/cyclophosphamide group. Adverse events were more frequent with tucotuzumab/cyclophosphamide (92.2%) than with BSC (47.7%). Tucotuzumab/cyclophosphamide was well tolerated in ED-SCLC patients, but did not show PFS or OS benefits compared with BSC. The observed trend toward prolonged PFS and OS in the subgroup of patients receiving previous PCI may support further confirmation in a larger population.

01 Dec 2013·BMC CancerQ2 · MEDICINE

A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors

Q2 · MEDICINE

ArticleOA

Author: Jean Henslee-Downey ; Lionel D Lewis ; Sarah Stewart ; Nancy L Lewis ; Daniel Kramer ; Josephine Harter ; Roger Stupp ; Roland Neugebauer ; Joseph P Connor ; Mildred Felder ; Philip B Komarnitsky ; Maria R Mattiacci ; Mihaela C Cristea

BACKGROUNDHumanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.METHODSPhase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.RESULTSTwenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m2 cyclophosphamide was 3.0 mg/m2. At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients.CONCLUSIONThe combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles.

01 Dec 2011·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interface

Q2 · MEDICINE

Article

Author: Paul M. Sondel ; Brian Gadbaw ; Stephen D. Gillies ; Arvinder K. Kapur ; Manish S. Patankar ; Sachi Horibata ; Dhara Patel ; Joseph Connor ; Jennifer A. A. Gubbels ; Ilia N. Buhtoiarov ; Jacquelyn A. Hank

The huKS-IL2 immunocytokine (IC) consists of IL2 fused to a mAb against EpCAM, while the hu14.18-IL2 IC recognizes the GD2 disialoganglioside. They are under evaluation for treatment of EpCAM(+) (ovarian) and GD2(+) (neuroblastoma and melanoma) malignancies because of their proven ability to enhance tumor cell killing by antibody-dependent cell-mediated cytotoxicity (ADCC) and by antitumor cytotoxic T cells. Here, we demonstrate that huKS-IL2 and hu14.18-IL2 bind to tumor cells via their antibody components and increase adhesion and activating immune synapse (AIS) formation with NK cells by engaging the immune cells' IL-2 receptors (IL2R). The NK leukemia cell line, NKL (which expresses high affinity IL2Rs), shows fivefold increase in binding to tumor targets when treated with IC compared to matching controls. This increase in binding is effectively inhibited by blocking antibodies against CD25, the α-chain of the IL2R. NK cells isolated from the peritoneal environment of ovarian cancer patients, known to be impaired in mediating ADCC, bind to huKS-IL2 via CD25. The increased binding between tumor and effector cells via ICs is due to the formation of AIS that are characterized by the simultaneous polarization of LFA-1, CD2 and F-actin at the cellular interface. AIS formation of peritoneal NK and NKL cells is inhibited by anti-CD25 blocking antibody and is 50-200% higher with IC versus the parent antibody. These findings demonstrate that the IL-2 component of the IC allows IL2Rs to function not only as receptors for this cytokine but also as facilitators of peritoneal NK cell binding to IC-coated tumor cells.

100 Deals associated with Tucotuzumab celmoleukin

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External Link

KEGG	Wiki	ATC	Drug Bank
D09027	Tucotuzumab celmoleukin	-	DB15402

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent ovarian cancer	Phase 2	-	EMD Serono, Inc.	31 Dec 2006
Prostatic Cancer	Phase 2	Switzerland	EMD Serono, Inc.	01 May 2005
Bladder Cancer	Phase 2	United States	EMD Serono, Inc.	01 Dec 2000
Kidney Neoplasms	Phase 2	United States	EMD Serono, Inc.	01 Dec 2000
Refractory Cancer	Phase 2	United States	EMD Serono, Inc.	01 Dec 2000
Ovarian Cancer	Phase 2	United States	EMD Lexigen Research Center Corp.	-
Ovarian Cancer	Phase 2	United States	EMD Lexigen Research Center Corp.	-
Small Cell Lung Cancer	Phase 2	United States	Merck KGaA	-
Small Cell Lung Cancer	Phase 2	-	EMD Lexigen Research Center Corp.	-
Small Cell Lung Cancer	Phase 2	-	Merck Serono SA	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2012	Phase 2	Extensive stage Small Cell Lung Cancer	108	huKS-IL2/CTX	khsjacrero(yhikranhoh) = njdvhkqobs mgnzspoxpr (qicezraxtd ) View more	-	20 May 2012
ASCO2011	Phase 1	EpCAM positive Solid Tumors	27	EMD 273066 (huKS-IL2) + cyclophosphamide	(tqpmvrphdc) = mwolvzeodt biyerkroau (yaarfdetai ) View more	-	20 May 2011

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Translational Medicine

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Approval

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Biosimilar

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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

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Tucotuzumab celmoleukin

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation