Largest Lung Cancer Study, MAGRIT, Shows Collective Commitment To Development Of Tailored Cancer Therapy

Main Category: Lung Cancer
Also Included In: Cancer / Oncology
Article Date: 05 Aug 2009 - 7:00 PDT

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Data presented on Sunday at the The International Society of Lung Cancer (IASLC) 13th World Conference on Lung Cancer (WCLC) in San Francisco highlight the screening of over 3,000 patients for MAGRIT (MAGE-A3 as Adjuvant Non-Small Cell LunG CanceR ImmunoTherapy)1, the largest-ever treatment trial in lung cancer. The rapid screening of patients into the MAGRIT trial is unprecedented given so few eligible lung cancer patients (less than 1% in the U.S.2) traditionally enter clinical trials and benefit from the potential hope of novel treatments.

MAGRIT is a phase III study investigating the efficacy of MAGE-A3 (Melanoma AntiGEn-A3) Antigen-Specific Cancer Immunotherapeutic (ASCI) in preventing cancer relapse, when given after tumor resection in patients with MAGE-A3-positive stages IB, II and IIIA Non-Small Cell Lung Cancer (NSCLC). The large trial population also provides a unique opportunity for translational research on other important questions about the prognosis and treatment of NSCLC.

"This screening rate for MAGRIT is exceptional given the challenges of such a large lung cancer trial and is a testament to the commitment of patients, the investigational site and GSK teams to the challenge of finding new ways to beat cancer," said Dr De Pas**, Medical Oncology Unit of respiratory Tract and Sarcomas, European Institut of Oncology, Milan, Italy "We are now working hard to build on this outstanding progress to accelerate study recruitment and answer as soon as we can how MAGE-A3 ASCI might help lung cancer patients."

As about a third of NSCLC tumors are MAGE-A3 positive, it is estimated that 3 times as many patients will need to be screened for MAGRIT, compared to clinical studies for non-specific therapies.

Current treatments are not optimal for the vast majority of patients with NSCLC. Surgical resection is the cornerstone of treatment for patients with early NSCLC, but relapse is high with 50-60% resected still dying of this disease3,4. Therefore the US National Cancer Institute recommends that patients should be considered for clinical trials 5.

Doctor-patient discussions on potential clinical trials, with referral to clinical trials sites as appropriate, are key to maximizing this opportunity for patients. Recruitment into the MAGRIT study continues and additional sites are also being actively sought, with a target of over 400 sites in 33 countries across the world.

"The rapid screening of over 3,000 patients into the MAGRIT study is an important step towards determining how patients may benefit from a potential new treatment for this challenging disease," said Dr. Vincent Brichard, Vice-President, Head of Cancer Immunotherapeutics at GSK Biologicals. "Tailored therapy with MAGE-A3 ASCI based on selecting NSCLC patients who's tumor is MAGE-A3 positive has the potential to improve clinical outcomes for these patients."

The preliminary data presented at the WCLC also confirm the feasibility and ease of large scale MAGE-A3 screening. The findings also support the previously reported MAGE-A3 tumor expression rates for NSCLC6 (about 35%), validating MAGE-A3 as a truly patient-selective, tumor-specific target.

Websites have been created to provide information on ASCI and the MAGRIT trial including site locations to patients, their family and the healthcare professionals. For more information please visit:

• http://www.immunotherapyforcancer.info


• http://www.asci-trials.com


• http://www.gsk-asci.com

About ASCIs and MAGE-A3 ASCI

• GSK's ASCIs represent a novel class of investigational medicines designed to train the immune system to recognize and eliminate cancer cells in a highly specific manner. These novel cancer immunotherapeutics combine tumor-specific antigens, delivered as purified recombinant proteins, and GSK's proprietary Adjuvant Systems, which are specific combinations of immunostimulating compounds designed to increase the anti-tumor immune response. ASCIs are being evaluated for use to reduce the risk of tumor recurrence following surgery, or to impact tumor growth in an early metastatic setting.


• MAGE-A3 is a tumor-specific antigen that is expressed in a large variety of cancers, including melanoma, non-small cell lung cancer, head and neck cancer and bladder cancer, with no expression in normal cells6,7. Expression of the MAGE-A3 gene has been observed in testicular cells but without antigen presentation capabilities8. It is anticipated that the high specificity of MAGE-A3 ASCI will target only cancer cells and will not harm normal tissue9. This is being confirmed in further clinical study.


• MAGE-A3 ASCI is also being evaluated in Phase III in melanoma (DERMA trial).

About MAGRIT

• MAGRIT was initiated following encouraging results from a Phase II proof-of-concept trial that investigated adjuvant therapy with MAGE-A3 ASCI in 182 patients with completely resected stage IB or II NSCLC6. A specific gene expression signature was also identified which might be predictive of benefit from MAGE-A3 ASCI treatment10. These findings will need to be confirmed in future clinical studies.


• The MAGRIT trial began recruiting in October 2007 and aims to randomize 2,270 patients from around 400 participating centers in 33 countries in Europe, North and South America, Asia and Australia.


• Patients will be selected for MAGRIT based on MAGE-A3 expression on the primary tumor.


• Eligible patients are randomized to ASCI or placebo; two patients will receive ASCI for every one that receives placebo.


• The study will include patients who have received surgery with or without standard adjuvant chemotherapy.


• The primary endpoint is disease-free survival.


• Treatment will be administered as 13 intramuscular injections over 27 months. Patients will be followed up every six months for five years, and then annually until 10 years from the start of treatment.

About Lung Cancer and NSCLC

• Lung cancer is the leading cause of global cancer mortality with an expected five year survival of only 15%11. Despite progress in the understanding of lung cancer, the incorporation of modern chemotherapy regimens and advances in supportive care, there has been no real improvement in patient survival from a rate of 13% in 197511,12.


• The majority of lung cancer cases are linked to smoking13. This often results in a stigma associated with diagnosis and can lead to difficulty with acceptance of treatment.


• Non-small cell lung cancer is the most common type of lung cancer, accounting for 80-85% of all cancers14, for which the main treatment is surgery alone, or with chemotherapy/radiotherapy15,16.


• Treatment of lung cancer is a major global challenge. However, ongoing research has identified targets for the immune system on cancer cells, and this has led to the development of cancer immunotherapy.

References
1. Tommaso De Pas., et al, MAGRIT Phase III trial in adjuvant NSCLC: MAGE-A3 gene expression frequency on the first 2150 patients screened and demographics of first patients randomized. Abstract B4.3, presented at International Association for the Study of Lung Cancer's 13th World Conference on Lung Cancer (WCLC), 2nd August 2009, San Francisco.
2. Feins,. Clinical Trials in Lung Cancer: Truth, Justice, and the American Way. Ann Thorac Surg 2000;70:1139-41.
3. The International Adjuvant Lung Cancer Trial Collaborative Group, Cisplatin-Based Adjuvant Chemotherapy in Patients with Completely Resected Non-Small-Cell Lung Cancer. N Engl J Med. 2004;350;351-6
4. Scagliotti., et al. Randomized Study of Adjuvant Chemotherapy for Completely Resected Stage I, II, or IIIA Non-Small-Cell Lung Cancer. Journal of the National Cancer Institute, 2003;95;1453-61.
5. National Cancer Institute. Non-small cell lung cancer treatment (PDQ): general information. http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/HealthProfessional/page2. Last accessed 23 June 2009.
6. Vansteenkiste J.,et al. Final results of a multi-center, double-blind, randomized, placebo controlled Phase II study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II Non-Small Cell Lung Cancer (NSCLC). J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I 2007; 25 (June 20 Suppl): 7554.
7. Van den Eynde BJ, van der Bruggen P. T cell defined tumor antigens. Curr Opin Immunol 1997;9:684-93 8. De Plaen E., et al. Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics 1994;40:360-9.
9. Boel P., et al. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 1995;2:167-75
10. Vansteenkiste JF., et al. Association of gene expression signature and clinical efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II non-small cell lung cancer (NSCLC). J Clin Oncol 2008b; 26 (suppl), abs 7501.
11. Garcia M., et al. Global Cancer Facts & Figures 2007. Atlanta, GA: American Cancer Society, 2007.
12. Katzel JA, Fanucchi MP, Li Z. Recent advances of novel targeted therapy in non-small cell lung cancer. J Hematol Oncol 2009;2:2
13. Molina JR., et al. Non-small cell lung cancer: epidemiology, risk factors treatment, and survivorship. Mayo Clin Proc 2008;83:584-94.
14. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008;359:1367-80.
15. National Collaborating Centre for Acute Care. Diagnosis and treatment of lung cancer. London: National Collaborating Centre for Acute Care, 2005.
16. Ramalingam S, Belani C. Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions. Oncologist 2008;13 Suppl 1:5-13.

Source
GlaxoSmithKline

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