MAGE-A3 vaccin leek hoopvol voor niet-klein-cellige longkanker, maar faalt in fase III studie en studie wordt stopgezet door GSK

7 april 2014: voor laatste stand van zaken betreffende immuuntherapie bij longkanker zie deze twee studies. Echter het laatste nieuws over stopzetten MAGE-3 vaccin, zie hieronder is daarin nog niet meegenomen: Immuuntherapie bij gevorderde niet-klein-cellige longkanker lijkt een goede aanpak te kunnen worden in de nabije toekomst en deze: Immuuntherapie bij longkanker: overzicht van stand van zaken aan de hand van studieresultaten van laatste 10 jaar

7 april 2014: Bron: persbericht GSK

Na teleurstellende resultaten uit een fase III studie heeft GlaxoSmithKline (GSK), producent van het Mage-3 vaccin besloten om studies met Mage-3 vaccin bij longkanker stop te zetten.

GSK announced its decision to stop the MAGRITi trial, a Phase III trial of its MAGE-A3ii cancer immunotherapeuticiii in non-small cell lung cancer (NSCLC) patients, after establishing that it will not be possible to identify a sub-population of gene-signature positive NSCLC patients that may benefit from the treatment.

Hier het persbericht van GSK van 2 april 2014: Update on phase III clinical trial of investigational MAGE-A3 antigen-specific cancer immunotherapeutic in non-small cell lung cancer

Onderaan staat volldige persbericht van fase III studie waarvan een abstract of het volledige studierapport nog niet aanwezig zijn, klik op persbericht van GSK over teleurstellende resultaten van fase III studie: A double-blind, randomized, placebo-controlled Phase III study to assess the efficacy of recMAGE-A3 + AS15 Antigen-Specific Cancer Immunotherapeutic as adjuvant therapy in patients with resectable MAGE-A3-positive Non-Small Cell Lung Cancer

15 juni 2012: voor laatste stand van zaken betreffende immuuntherapie bij longkanker zie deze twee studies: Immuuntherapie bij gevorderde niet-klein-cellige longkanker lijkt een goede aanpak te kunnen worden in de nabije toekomst en deze: Immuuntherapie bij longkanker: overzicht van stand van zaken aan de hand van studieresultaten van laatste 10 jaar

15 juni 2012: Als u wilt deelnemen aan onderstaande studie naar immuuntherapie bij longkanker met MAGE-A3 neem dan contact op met het oncologisch centrum van de universiteit van Leuven.

Klik hier voor de criteria waaraan u moet voldoen om in aanmerking te komen voor studiegroep:

21 juni 2006: Bron: Medscape

Een vaccin onder de naam MAGE-A3 zou in een fase II trial bemoedigende resultaten hebben laten zien in het voorkomen van een recidief van geopereerde niet-klein-cellige longkankerpatienten welke dit gen, MAGE-A3, bij zich dragen. De studie is uitgevoerd in Brussel/Leuven. Van geopereerde longkankerpatienten met als doel genezing krijgt volgens de onderzoekers statistisch gezien gemiddeld de helft een recidief. Met deze vaccinatie bleek slechts 33% van de deelnemende patienten een recidief te krijgen. Plus dat het vaccin goed werd verdragen. Slechts 2 patienten haakten af, alle anderen van de 182 deelnemende patienten bleek beschikbaar voor de tussenevaluatie van de studie, welke tussenvaluatie op 21 maanden werd uitgevoerd.

Het primaire einddoel voor de studie was de tijd tot een recidief. Patienten werden gevaccineerd binnen 6 weken na de operatie met 5 vaccinaties in een 3 wekelijks interval schema, gevolgd door 8 vaccinaties elke 3 maanden.

De vooraf geplande tussenanalyse werd geuitgevoerd na een studieperiode van 21 maanden. Op dt moment hadden 37 van de 122 patienten (30.3%) die het specifieke antigene immunotherapeutische MAGE-A3 (ASCI) hadden gekergen een recideif, in vergelijking met 25 van de 60 patienten (41.7%) die een placebo hadden gekregen. De onderzoekers gebruikten een Cox regressie model om een en ander geljik te trekken en te kunnen vergelijken omdat de patienten op verschillende tijden en in verschillende groepen begonnen met de studie. Zij constateerden een 33% verminderd relatief risico op een recidief, welke echter niet statistische significant is (P = .121).

Toch blijkt dit een bemoedigend resultaat en worden er nu fase III studies opgezet. Wie dus in Belgie of Nederland woont zou dit in de gaten kunnen houden om eventueel deel te nemen aan deze studie.

Lung Cancer Vaccine Shows Promise

Allison Gandey

June 19, 2006 (Atlanta) — Researchers are hunting for alternatives to adjuvant cisplatin-based chemotherapy, because postoperative tolerance after lung resection is low. They say a new vaccine may soon offer patients with non–small cell lung cancer another, less-toxic option. The team presented findings at the recent 42nd annual meeting of the American Society of Clinical Oncology.

In this phase 2, randomized, placebo-controlled clinical trial, patients had tumors expressing a tumor-specific antigen known as MAGE-A3, which is present in approximately 35% to 50% of early non–small cell lung cancers. The researchers studied 182 patients who received either GlaxoSmithKline's new MAGE-A3 vaccine or placebo. The investigational product is not approved for use in any country at this time.

"Tolerance was indeed excellent," lead author Johan Vansteenkiste, MD, from the University Hospital Gasthuisberg Herestraat in Leuven, Belgium, told Medscape. "The most commonly reported adverse events were mild local or systemic reactions observed within 24 hours of injection. Of 182 patients, only 2 patients were withdrawn from the clinical trial due to adverse events possibly related to the MAGE-A3 treatment."

According to the research team, about half of patients with completely resected early-stage non–small cell lung cancer will relapse. While adjuvant chemotherapy has gained popularity in recent years for reducing the number of relapses, this has been at the expense of substantial toxicity. Vaccines such as the one proposed in this study are designed to stimulate the patient's own immune response to attack cancer cells in a highly specific manner.

"This trial demonstrates the feasibility of developing novel cancer immunotherapies that with continuing research may expand into a new approach to cancer treatment," Paul Bunn, MD, from the University of Colorado Cancer Center in Denver, said in a news release about the study. "It represents an important step not only in finding better therapy for the most common type of lung cancer but also in exploring the broader potential of these compounds."

Failed to Meet Statistical Significance but Warrants Further Study

The primary end point for the trial was time to recurrence. Patients were vaccinated at least 6 weeks after surgery with 5 vaccinations at 3-week intervals, followed by 8 vaccinations every 3 months.
,br> The preplanned interim analysis was performed at a median follow-up of 21 months. At this time, 37 of the 122 patients (30.3%) receiving MAGE-A3 antigen specific cancer immunotherapeutic (ASCI) had relapsed compared with 25 of the 60 patients (41.7%) receiving placebo . The researchers used a Cox regression model to adjust for the fact that patients in the different groups were enrolled in the study at different times. They observed a 33% reduction in relative risk of cancer recurrence, which did not meet statistical significance (P = .121).

"It is not the aim of a phase 2 randomized study to deliver definite proof a new therapeutic strategy," Dr. Vansteenkiste told Medscape. "The finding is, however, very encouraging and warrants continued investigation."

According to a company news release, efficacy results of the interim analysis will be available in February 2007. The full analysis will focus on time to recurrence, disease-free survival, overall survival, and lung cancer–related death rate, as well as safety and immunogenicity. Phase 3 trials are planned to begin early next year.

"These first results obtained with our MAGE-A3 ASCI reinforce our belief in the potential application of the ASCI approach in the treatment of cancer," Mr. Jean Stéphenne, president of GlaxoSmithKline biologicals, told reporters.

In addition to MAGE-A3, the company is looking at a variety of other tumor antigens using the same approach. "We are confident in our ability to develop a rich pipeline of ASCIs targeting in a highly specific manner many types of cancers."

ASCO 42nd Annual Meeting: Abstract 7019. Presented June 4, 2006.

Investigational MAGE-A3 antigen-specific cancer immunotherapeutic does not meet first co-primary endpoints in MAGRIT, a phase III non-small cell lung cancer clinical trial

Issued: 2 April 2014, London UK and Issued: Thursday 20 March 2014, London UK

Source: GSK

Issued: Thursday 20 March 2014, London UK

GSK will continue the trial in order to assess the third co-primary endpoint, which is disease-free survival in a gene signature positive sub-population

GlaxoSmithKline plc (LSE:GSK) today announced that analysis of the MAGRITⁱ trial, a phase III trial of its MAGE-A3 cancer immunotherapeuticⁱⁱ in non-small cell lung cancer (NSCLC) patients, showed that the trial did not meet its first or second co-primary endpoint as it did not significantly extend disease-free survival (DFSⁱⁱⁱ) when compared to placebo in either the overall MAGE-A3 positive population (first co-primary endpoint) or in those MAGE-A3-positive patients who did not receive chemotherapy (second co-primary endpoint). GSK currently remains blinded to the overall trial data from the analysis of the first two co-primary endpoints to allow for the unbiased generation of a mathematical model to assess the third co-primary endpoint^iv.

MAGRIT, a randomised, double-blind, placebo-controlled trial, is evaluating the efficacy and safety of the MAGE-A3 cancer immunotherapeutic in Stage IB, II and IIIA completely resected NSCLC patients whose tumours expressed the MAGE-A3 gene. Patients were given up to 13 intramuscular injections of either the MAGE-A3 immunotherapeutic or placebo over a period of 27 months.

MAGE-A3 is a tumour-specific antigen expressed in a variety of cancers but not in normal cells. In NSCLC, it is expressed in approximately one third of tumours in patients diagnosed with Stage IB-IIIA disease. The MAGRIT trial enrolled 2,312 MAGE-A3-positive patients across more than 400 sites in 34 countries worldwide.

The Independent Data Monitoring Committee (IDMC) indicated that its review of the current safety information raised no specific concern for the continuation of the trial and is in line with the known safety information for the MAGE-A3 cancer immunotherapeutic. As planned GSK will continue the trial in order to assess the third co-primary endpoint. This endpoint is designed to identify a subset of MAGE-A3 positive patients that may benefit from the treatment with the MAGE-A3 cancer immunotherapeutic. Results from a final analysis are expected in 2015.

Vincent Brichard, Senior Vice-President & Head of Immunotherapeutics, GSK Vaccines said: “We want to thank all patients, their families and healthcare workers for their involvement in the MAGRIT trial. We are disappointed that the trial did not demonstrate a benefit for overall MAGE-A3 positive patient population, but we remain committed to the effort to identify a sub-population of NSCLC patients who may benefit from this investigational treatment.”

MAGE-A3, vaccin, immuuntherapie, melanomen, longkanker