Delving into the Latest Updates on Ecromeximab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Ecromeximab (USAN/INN)

Target

GD3

Mechanism

GD3 inhibitors(Ganglioside GD3 inhibitors), Immunostimulants

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

MelanomaMelanoma, Cutaneous MalignantMetastatic melanoma

Originator Organization

Kyowa Kirin Co., Ltd.

Active Organization-

Inactive Organization

Kyowa Kirin, Inc. /Sancuso/

Ludwig Institute for Cancer Research Ltd.Kyowa Kirin Pharmaceutical Development Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 319922110L

Source: *****

Sequence Code 319922109H

Source: *****

This was a Phase 2, open-label study of KW2871 (ecromeximab) in combination with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. The primary objectives of this study were to assess progression-free survival (PFS) and safety. The secondary objectives were to assess the objective response rate, KW2871 pharmacokinetics (PK), and other exploratory immunology as indicated (e.g., development of human anti-chimeric antibodies [HACA], activity of antibody-dependent cell-mediated cytotoxicity [ADCC] and complement-dependent cytotoxicity [CDC] in peripheral blood, number and functional state of tumor-infiltrating immune cells and expression of GD3 in immune and tumor cells of tumor biopsies, and markers of interferon [IFN] response/resistance and markers of resistance to ADCC/CDC in peripheral blood mononuclear cells [PBMCs]).

Start Date28 Mar 2008

Sponsor / Collaborator

Ludwig Institute for Cancer Research Ltd.

[+3]

NCT00199342 / TerminatedPhase 1/2

An Open-Label Study of KW-2871 Administered With a Premedication Regimen in Patients With Advanced Stage IV Melanoma

This is a dose escalating cohort study to determine the maximum tolerated dose (MTD) of KW-2871 (in dose cohorts of 60, 80, and 100 mg/m2) when administered with a specified premedication regimen (ranitidine, diphenhydramine, and dexamethasone). KW-2871 will be administered at 14-day intervals.

Start Date01 Nov 2004

Sponsor / Collaborator

Kyowa Kirin, Inc. /Sancuso/

100 Clinical Results associated with Ecromeximab

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100 Translational Medicine associated with Ecromeximab

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100 Patents (Medical) associated with Ecromeximab

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3

Literatures (Medical) associated with Ecromeximab

01 Aug 2017·Melanoma ResearchQ4 · MEDICINE

Safety and efficacy of the antiganglioside GD3 antibody ecromeximab (KW2871) combined with high-dose interferon-α2b in patients with metastatic melanoma

Q4 · MEDICINE

Article

Author: Lin, Hui-Min ; Yin, Yan ; Gajewski, Thomas F. ; Kirkwood, John M. ; Venhaus, Ralph ; Sander, Cindy ; Moschos, Stergios J. ; Lin, Yan ; Tarhini, Ahmad A.

This study evaluated the safety and clinical benefit of ecromeximab (KW2871) combined with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. We also carried out pharmacokinetic and immune monitoring studies of this combination. This was an open-label, phase 1/2 study of ecromeximab plus HDI in patients with measurable metastatic melanoma. Eligible patients received ecromeximab-HDI combination therapy: ecromeximab administered intravenously once every 2 weeks and HDI at a dose of 20 million units (MU)/m2 administered intravenously for 5 consecutive days per week for the first 4 weeks (induction phase) and then at 10 MU/m2 subcutaneously thrice weekly through week 14 (maintenance phase). Patients were treated with combination therapy until disease progression or limiting toxicity. Three dose-escalation cohorts (5, 10, and 20 mg/m2) of ecromeximab were planned. Thirty-six evaluable patients were enrolled including six in each of cohorts 1 and 2, and 24 in cohort 3. Median progression-free survival was 2.53 months [95% confidence interval (CI):1.93–3.83] and it was 1.93 months (95% CI: 1.00–3.80) in cohort 3. The median overall survival was 10.28 months (95% CI: 6.93–16.77) and 7.78 months (95% CI: 6.03–13.97) in cohort 3. There was no significant difference in progression-free survival or overall survival by BRAF mutation status. The response rate was 5.6% (95% CI: 0.68–18.7), with two patients showing an objective response (one complete response and one partial response), and the clinical benefit rate was 78% (95% CI: 61–90). Stable disease as best response was observed in 26 (72%) patients including five in each of cohorts 1 and 2, and 16 in cohort 3. Treatment-emergent adverse events considered related to ecromeximab treatment occurred in four (66.7%) patients in cohort 1, five (83.3%) patients in cohort 2, and seven (29.2%) patients in cohort 3. Among TEAEs with a maximum severity of grade 3 or 4, those that occurred only in cohort 3 were related to pain, electrolyte imbalance, blood cell decreases, and allergic reaction. Safety and efficacies considered related to ecromeximab occurred in cohort 3 and included grade 3 hypersensitivity [one (4.2%)] and grade 2 hypotension [one (4.2%)]. Regimen-limiting toxicities occurred in two (8.3%) patients in cohort 3: hypersensitivity (with hypertension, supraventricular tachycardia, bronchospasm, chills, and dyspnea) and hypotension. One patient out of 31 examined showed a low-level transient positivity for human antichimeric antibodies against ecromeximab. Pharmacokinetic measurements by enzyme-linked immunosorbent assay determined that administration of HDI does not influence serum levels of ecromeximab at 5, 10, and 20 mg/m2 dose levels. Ecromeximab in combination with HDI was generally well tolerated in patients with metastatic melanoma and has shown low immunogenicity. However, the clinical activity was limited, suggesting that future development of this combination should be deprioritized and that other combinations, such as with immune checkpoint inhibitors, should be considered.

01 Dec 2006·Cancer Biotherapy and RadiopharmaceuticalsQ4 · MEDICINE

Anti-GD3 Monoclonal Antibody Effects on Lymphocytes and Antibody-Dependent Cellular Cytotoxicity

Q4 · MEDICINE

Article

Author: LoBuglio, Albert F. ; Su, Kaihong ; Triozzi, Pierre L. ; Conry, Robert ; Aldrich, Wayne ; Carlisle, Ronda ; Edberg, Jeffrey C. ; Forero, Andres ; Wang, Wen-Quan ; Shah, Jatin J.

PURPOSEAntibodies targeting GD3 gangliosides highly expressed on melanomas mediate immune effector functions in vitro and inhibit animal model melanoma tumor growth in vivo. Because GD3 is expressed also on a subpopulation of human lymphocytes, we characterized the in vitro immune effects of murine R24 and a chimeric anti-GD3 antibody (KW-2871).DESIGNAnti-GD3 complement-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested against cell line Mel-624. Antibody-mediated lymphocyte expression of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) was quantified. The effect of antibody and antibody-treated lymphocyte supernates on effector cell ADCC and Fc receptor expression were evaluated.RESULTSR24 and KW-2871 antibodies mediated CMC and ADCC to the Mel-624 cell line. R24 induced potent lymphocyte proliferation and enhanced lymphocyte RNA expression of IL-4 (2-4 logs), IL-10, and IFN-gamma (> 10-fold). KW-2871 induced no lymphocyte proliferation and had minimal effects on lymphokine expression (< 5-fold). Preincubation of effector cells with either antibody inhibited ADCC and reduced monocyte expression of FcgammaRI and II. Supernates of effector cells preincubated with either antibody were able to inhibit ADCC.CONCLUSIONSR24 and KW-2871 antibody differ in their lymphocyte proliferation and lymphokine release activity but have similar inhibition of lymphocyte ADCC and FcgammaR expression in vitro.

01 Dec 2006·Cancer Biotherapy and RadiopharmaceuticalsQ4 · MEDICINE

A Phase I Study of an Anti-GD3 Monoclonal Antibody, KW-2871, in Patients with Metastatic Melanoma

Q4 · MEDICINE

Article

Author: Forero, Andres ; Shah, Jatin ; Triozzi, Pierre L. ; Conry, Robert M. ; Carlisle, Ronda ; Fujimori, Matt ; Wang, Wen-Quan ; LoBuglio, Albert F.

PURPOSEKW-2871 (IgG1 kappa chimeric antibody) targets GD3, which is upregulated in melanomas. We conducted a phase I trial of KW-2871 in patients with metastatic melanoma.METHODSSeventeen (17) patients were enrolled and received an initial test dose (10 mg/m2) intravenously. Two 2 weeks later, patients were stratified into 4 cohorts to receive 4 doses of KW-2871 (infused over 1 hour) at 2-week intervals (20, 40, 60, and 80 mg/m2). No premedications were administered for the test or first therapeutic doses.RESULTSDose-limiting toxicities were Grade 3 laryngospasm and chest tightness with the initial therapeutic infusion at doses of 80 and 60 mg/m2. The maximum tolerated dose (MTD) was established at 40 mg/m2 of KW2871. The most common side-effect was urticaria (Grades 1-3) in 16 of 16 patients during an initial therapeutic infusion without premedication. The mean terminal half-life, clearance, and area under the concentration-time curve (AUC(0-t)) at a dose of 40 mg/m2 for course 1 were 146 +/- 31 hours, 28 +/- 6 ml/hour, and 1922 +/- 491 mcg*hour/mL, respectively. Anti-human chimeric antibody was not detected. Two (2) patients in the 40 mg/m2 cohort had stable disease.CONCLUSIONSAn MTD of 40 mg/m2 without premedication was established for KW-2871, with urticaria being the most common side-effect and dose-limiting anaphylactoid infusion reactions.

100 Deals associated with Ecromeximab

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External Link

KEGG	Wiki	ATC	Drug Bank
D03939	Ecromeximab	-	DB12797

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma, Cutaneous Malignant	Phase 2	US	Ludwig Institute for Cancer Research Ltd.	28 Mar 2008
Melanoma	Phase 2	US	Kyowa Kirin Pharmaceutical Development Ltd.	01 Nov 2004
Metastatic melanoma	Phase 2	US	Kyowa Kirin, Inc. /Sancuso/	01 Nov 2004
Metastatic melanoma	Phase 2	US	Kyowa Kirin, Inc. /Sancuso/	01 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


NCT00679289 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Metastatic melanoma	36	HDI+KW2871 (Cohort 3)	njzdfmclmi(ktwdsakvqm) = dbvefuzpkk vzfkxycpom (qkgyzqcpqp, gydwlqychr - qghnwjmrbb) View more	-	09 Feb 2018
NCT00679289 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Metastatic melanoma	36	HDI+KW2871 (Cohort 1)	olscprqqiq(puwrefnmlx) = vcuhrauoxm zwfzzahxig (vakpitkpbq, bjgfxuvrgl - rwyzbngcvu) View more	-	09 Feb 2018
NCT00679289 (Pubmed \| Melanoma Res)	Phase 1/2	Metastatic melanoma	36	Ecromeximab	(wznnjdxwkp) = iygncclofr celphpdekk (mvqdtlaayh ) View more	-	01 Aug 2017
ASCO2005	Phase 1	Metastatic melanoma	17	KW-2871 40 mg/m2	(kvqaojchbp) = kqbmakoryq mjwbcurzpv (axlolbbhun ) View more	-	01 Jun 2005