Delving into the Latest Updates on GM2-KLH vaccine(Memorial Sloan Kettering Cancer Center) with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine

Synonyms

Target-

Action

stimulants

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Breast CancerMelanoma, Cutaneous Malignant

Originator Organization

Memorial Sloan Kettering Cancer Center

Active Organization-

Inactive Organization

Eortc

Memorial Sloan Kettering Cancer Center

License Organization-

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than observation alone for melanoma.
PURPOSE: This randomized phase III trial is studying vaccine therapy to see how well it works compared to observation alone in treating patients with primary stage II melanoma.

Start Date01 Dec 1999

Sponsor / Collaborator

Eortc

NCT00003357

/ CompletedPhase 1IIT

Vaccination of High Risk Breast Cancer Patients Lacking Identifiable Disease With GM2-KLH Conjugate Plus the Immunological Adjuvant QS21

RATIONALE: Vaccines made from GM2-KLH and given with QS21 may make the body build an immune response to and kill tumor cells.
PURPOSE: Phase I trial to study the effectiveness of GM2-KLH vaccine plus QS21 in treating patients with breast cancer who have no evidence of disease.

Start Date01 Jan 1998

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

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100 Clinical Results associated with GM2-KLH vaccine(Memorial Sloan Kettering Cancer Center)

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100 Translational Medicine associated with GM2-KLH vaccine(Memorial Sloan Kettering Cancer Center)

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100 Patents (Medical) associated with GM2-KLH vaccine(Memorial Sloan Kettering Cancer Center)

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12

Literatures (Medical) associated with GM2-KLH vaccine(Memorial Sloan Kettering Cancer Center)

03 Jun 2018·OncoImmunologyQ2 · MEDICINE

Multiplex bead-based measurement of humoral immune responses against tumor-associated antigens in stage II melanoma patients of the EORTC18961 trial

Q2 · MEDICINE

ArticleOA

Author: Eichmüller, Stefan B. ; Becker, Natalia ; Jäger, Dirk ; Benner, Axel ; Suciu, Stefan ; Halama, Niels ; Zörnig, Inka ; Agoussi, Sandrine ; Pawlita, Michael ; Eggermont, Alexander M. M. ; Kaiser, Iris ; Waterboer, Tim ; Kosaloglu-Yalcin, Zeynep ; Michels, Judith

Purpose: Determine the prognostic and predictive significance of tumor associated antigen (TAA)-specific serum antibodies in melanoma patients of a large adjuvant vaccination phase III trial. Patients and methods: Serum IgG antibodies were measured against a panel of 43 antigens by a bead-based multiplex assay in 970 stage II melanoma patients of the EORTC18961 trial, evaluating adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation. Primary end point was relapse-free survival (RFS). Patients' sera at baseline, after 12 and 48 weeks of study treatment and at the last available time point (at recurrence/remission) were evaluated. Results: Prognostic clinical variables are gender, surgical confirmation of lymph node-negative status, Breslow thickness and ulceration of the primary. Prognostic spontaneous antibody responses were associated with a significant dismal (GM2, Rhod_E2, SSX2) or good prognosis (CyclinB1, SCYE1v1) for RFS, distant metastasis-free (DMFS) or overall survival (OS). Predictive spontaneous antibody responses based on significant interaction with treatment were RhodN p = 0.02, Rab38 p = 0.04 for RFS, RhodE2 p = 0.006, Recoverin p = 0.04 for DMFS and RhodE2 p = 0.003; Recoverin p = 0.04, NA17.A p = 0.04, for OS respectively. The subgroups of patients according to antibody responses for RFS were determined for RhodN sero-negative (n = 849, HR = 1.07, p = 0.6); RhodN sero-positive (n = 121,HR = 0.42, p = 0.01) and Rab38 sero-negative (n = 682, HR = 1.12, p = 0.42), Rab38 sero-positive (n = 288, HR = 0.65, p = 0.04) patients respectively. Conclusion: We identified prognostic serum antibody responses against TAA in stage II melanoma patients. A set of antibody responses correlated with a beneficial outcome for GM2 vaccination.

01 Apr 2014·Melanoma ResearchQ4 · MEDICINE

Serologic evidence of autoimmunity in E2696 and E1694 patients with high-risk melanoma treated with adjuvant interferon alfa

Q4 · MEDICINE

Article

Author: Kirkwood, John M. ; Sander, Cindy A. ; Shin, Donghoon ; Lee, Sandra J. ; Tarhini, Ahmad A. ; Stuckert, Joseph

We evaluated Eastern Cooperative Group phase II and III trials E2696 and E1694 to assess the incidence and prognostic significance of autoimmunity induced by adjuvant high-dose interferon-α2b (HDI). In E2696, patients with resectable high-risk melanoma were randomized to receive vaccination with GM2-KLH/QS-1 (GMK) plus concurrent HDI, GMK plus sequential HDI, or GMK alone. E1694 randomized patients to either HDI or GMK. Sera from 103 patients in E2696 and 691 patients in E1694 banked at baseline and up to three subsequent time points were tested by ELISA for the development of five autoantibodies. In E2696, autoantibodies were induced in 16 patients (23.2%; n=69) receiving HDI and GMK and two patients (5.9%; n=34) receiving GMK alone (P=0.031). Of 691 patients in E1694, 67 (19.1%) who received HDI (n=350) developed autoantibodies, but only 16 patients (4.7%) developed autoantibodies in the vaccine group (n=341; P<0.001). Almost all induced autoantibodies were detected at ≥12 weeks after the initiation of therapy. A 1-year landmark analysis among resected stage III patients treated with HDI in E1694 showed a trend toward a survival advantage associated with HDI-induced autoimmunity (hazard ratio=0.80; 95% confidence interval: 0.50-1.98; P=0.33). Therefore, adjuvant HDI therapy is associated with the induction of autoimmunity that should be further investigated prospectively as a surrogate marker of adjuvant therapeutic benefit. This potential biomarker develops over the course of up to 1 year, and cannot be used to alter the course of therapy. Studies of the genetic determinants of this response may better discriminate patients more likely to benefit from HDI immunomodulatory therapy.

20 Oct 2013·Journal of Clinical OncologyQ1 · MEDICINE

Adjuvant Ganglioside GM2-KLH/QS-21 Vaccination Versus Observation After Resection of Primary Tumor > 1.5 mm in Patients With Stage II Melanoma: Results of the EORTC 18961 Randomized Phase III Trial

Q1 · MEDICINE

Article

Author: Ascierto, Paolo A. ; Patel, Poulam M. ; Aamdal, Steinar ; Rutkowski, Piotr ; Kruit, Wim H. ; Polders, Larissa ; Corrie, Philippa ; Suciu, Stefan ; Bernengo, Maria Grazia ; Santinami, Mario ; Bastholt, Lars ; Marsden, Jeremy ; Borgognoni, Lorenzo ; Praet, Michel ; Davidson, Neville ; Eggermont, Alexander M.M. ; Spatz, Alan

Purpose The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation. Patients and Methods A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat. Results After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity. Conclusion GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.

100 Deals associated with GM2-KLH vaccine(Memorial Sloan Kettering Cancer Center)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma, Cutaneous Malignant	Phase 3	United Kingdom	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Russia	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Spain	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Switzerland	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Denmark	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Portugal	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Finland	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Germany	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Israel	Eortc	01 Dec 1999
Melanoma, Cutaneous Malignant	Phase 3	Estonia	Eortc	01 Dec 1999

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EORTC 18961 (ASCO2010)	Phase 3	Melanoma Adjuvant	-	Ganglioside GM2-KLH/QS-21 vaccination	(txzohtblza) = vrzwwuohal urnetxunep (iyabsgxeap ) View more	Negative	20 May 2010
				ganglioside GM2-KLH/QS-21 vaccination (Observation)	(txzohtblza) = doeosjsode urnetxunep (iyabsgxeap ) View more