Elesclomol study shows a significant improvement in progression-free survival in patients with metastatic melanoma chemotherapy Naive

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This retrospective subgroup analysis of a randomized, double-blind, controlled phase II in patients with stage IV metastatic melanoma evaluated the rate of progression-free survival and overall survival for the combination of elesclomol and paclitaxel against paclitaxel alone in patients who received chemotherapy treatment with those who had never received chemotherapy. A total of 81 patients evaluated in this analysis either received 213 mg/m2 of elesclomol co-infused with 80 mg/m2 of paclitaxel 80 mg/m2 or paclitaxel alone in four week cycles (once weekly for three weeks and one week rest) until disease progression.1

“Metastatic melanoma is an aggressive tumor, and patients who currently have few treatment options,” said investigator David Lawson, MD, Emory University School of Medicine. “Identify new treatments such as elesclomol represent the future to deal with this hard-to-treat disease.”

FAQ melanoma (7). World Health Organization. http://www.who.int/uv/faq/skincancer/en/index1.html (April 17, 2008).

(9) United States Securities and Exchange Commission. Synta Pharmaceuticals Corp. Form 10-K. Annual report pursuant to Article 13 or 15 (d) of the Securities Exchange Act of 1934. Commission file number 002-33277. For the year ended December 31, 2007.

(8) Tarhini A, S. Agarwala cutaneous melanoma: available therapy for metastatic disease. Dermatologic Therapy. 2006; 19:19-25.

“The preliminary clinical data for elesclomol in patients with metastatic melanoma are encouraging and underline the urgent need for new therapies,” said Eric Jacobson, MD, Senior Vice President and Chief Medical Officer, Synta. “These data, combined with previous preclinical and clinical data we presented for elesclomol, confirm our belief that the induction of oxidative stress is a promising new approach to cancer therapy in melanoma and, potentially, other cancers” .

- Have you ever had a longer median progression-free survival (7.1 months versus 1.8 months, p = 0.020) 0.1

(4) What you should know about melanoma. National Cancer Institute. September 2002. http://www.cancer.gov/cancertopics/wyntk/melanoma (March 18, 2008).

Elesclomol is a novel, injectable, an investigational drug candidate that triggers apoptosis (programmed cell death) of cancer cells. Cancer cells operate at high levels of reactive oxygen species, or oxidative stress. Elesclomol is supposed to act by increasing the level of oxidative stress in cancer cells even further, beyond sustainable levels, inducing apoptosis. This mechanism of action, called oxidative stress induction, represents a new way of selectively targeting and killing cancer cells.

(1) Gonzalez R, Lawson D, et al. Al Final Poster for Abstract # 9036 Phase 2 Trial of Elesclomol (formerly STA-4783) and Paclitaxel in Stage IV metastatic melanoma (MM): analysis of the subgroup with prior chemotherapy. To be presented at the 2008 American Society of Clinical Oncology annual meeting.

Phase II study of paclitaxel and Elesclomol in stage IV metastatic melanoma: a subgroup analysis for chemotherapy (Abstract # 9036) Time of submission: May 31, 2008, 14:00 06:00

Synta Pharmaceuticals and GlaxoSmithKline are studying elesclomol in a global context, referred to as Phase III SYMMETRYSM essential. SYMMETRY The study is being conducted in approximately 150 centers worldwide to determine the efficacy of elesclomol in combination with paclitaxel for the treatment of patients with metastatic (stage IV) melanoma. 9 Elesclomol received Fast Track and Orphan Drug designation by the FDA for metastatic melanoma, and the stage of symmetry tour of 3 completed a Special Protocol Assessment process with the FDA. Further investigations to evaluate elesclomol as a therapy for other cancers are currently planned.9

- He lived an average of nearly six months longer (15.9 months versus 10.0 months)

Regardless of prior chemotherapy, the most common adverse events in the group elesclomol plus paclitaxel following: fatigue, alopecia, constipation, nausea, numbness, arthralgia, insomnia, diarrhea and anemia. The most serious adverse events (grade 3 or higher) for the combination arm were similar to those observed in the paclitaxel arm and included neutropenia, back pain, fatigue and neuropathy.1

Patients who had not received prior chemotherapy and received a combination of (n = 24) elesclomol and paclitaxel compared with patients who received paclitaxel alone (n = 8):

(3) The signs and symptoms of melanoma. University of CaliforniaSan FranciscoMedicalCenter. http://www.ucsfhealth.org/adult/medical_services/cancer/skin/conditionsMelanoma/signs.html (March 18, 2008).

The data for patients in the paclitaxel arm elesclomol and had prior chemotherapy showed a trend similar results for patients who have not received prior chemotherapy, but these data were not statistically significant. In particular, after having received prior chemotherapy, the median PFS was 2.8 months for patients (n = 29) and paclitaxel elesclomol against 1.8 months for patients on chemotherapy alone (n = 20, p = 0.552 ) and OS was 9.0 months for patients on elesclomol and paclitaxel versus 7.8 months in patients treated with paclitaxel alone.1

(10) J. Kirshner Elesclomol (formerly STA-4783) induces apoptosis and enhances antitumor activity of paclitaxel through induction of oxidative stress. Poster presented at the International Conference on molecular targets and Cancer Therapeutics: AACR-NCI-EORTC October 24, 2007.

“The incidence of melanoma has continued to increase in recent years and there is an urgent need to identify effective treatments for patients with metastatic disease,” said Paolo Paoletti, MD, Vice-President of Cancer Center Development Medicine GSK. “GSK is in the forefront of research to improve the lives of cancer patients, including those with limited treatment options, and we are committed to conducting ongoing trials in metastatic melanoma.”

GlaxoSmithKline one of the world’s leading research-based pharmaceutical and healthcare companies committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more company information, visit GlaxoSmithKline at http://www.gsk.com.

Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing and commercializing small molecule drugs to extend and improve the lives of patients suffering from serious health conditions, including cancer and chronic inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a diversified portfolio of clinical and preclinical drug center stage with the candidates distinct mechanisms of action and novel chemical structures. All Synta drug candidates were invented by Synta scientists using our compound library and drug discovery capabilities. Synta has a partnership with GlaxoSmithKline for the joint development and commercialization of its lead drug candidate, elesclomol, which is in a global Phase III clinical trials for the treatment of metastatic melanoma. For more information, please visit http://www.syntapharma.com.

Metastatic melanoma occurs when melanoma is a cancer that begins in melanocytes, the cells that produce the skin pigment, or spreads to other parts of melanin body.2, 3 in the U.S., the proportion of people who develop melanoma in the form deadly skin cancer has more than doubled in the last 30 years, and approximately 60,000 people diagnosed with melanoma and 8,000 will die 2008.4,5,6 in the world, about 132,000 new diagnoses are made each year7 There is currently no approved drugs that have shown improve survival in patients with metastatic melanoma.8

Synta Pharmaceuticals Corp. and GlaxoSmithKline today announced positive Phase II clinical elesclomol (formerly STA-4783), a research officer in development for metastatic melanoma. A retrospective analysis showed that patients with stage IV metastatic melanoma treated with paclitaxel and elesclomol had not received prior chemotherapy showed a statistically significant improvement in progression-free survival (PFS) than patients treated with paclitaxel These alone.1 I data will be presented at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Elesclomol has not yet been approved for any indications in any market.

Elesclomol was developed under a global collaboration agreement between Synta Pharmaceuticals and GlaxoSmithKline.

(2) Home melanoma. National Cancer Institute. http://www.cancer.gov/cancertopics/types/melanoma (March 18, 2008).

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