Synta Pharmaceuticals Corp. announced that the first patients have been treated in the Symmetry(SM) trial - Synta Metastatic Melanoma Elesclomol Trial - a global, pivotal phase II clinical trial to evaluate the safety and efficacy of elesclomol (formerly STA-4783) in patients with stage IV metastatic melanoma.
Synta also reported that it has successfully completed the Special Protocol Assessment (SPA) process, reaching agreement with the FDA on the design, conduct, and planned analyses of the trial.
Elesclomol is a novel, small molecule, first-in-class drug candidate, discovered and developed by Synta, that acts by elevating the level of oxidative stress of cancer cells beyond a breaking point, inducing programmed cell death. In a recently completed phase IIb double-blind, randomised, 21-centre clinical trial in metastatic melanoma, treatment with elesclomol doubled median progression-free survival - the time patients survived without worsening of disease - achieving the primary endpoint of the study to statistical significance.
In November 2006, Synta received Fast Track designation from the FDA for the development of elesclomol in metastatic melanoma. In October 2007, Synta announced a partnership with GlaxoSmithKline (GSK) to jointly develop and commercialize elesclomol.
"Metastatic melanoma is a devastating disease with a median survival of six to nine months and no improvement in standard of care in over 30 years," said Safi Bahcall, Ph.D., president and CEO, Synta. "Initiating the SYMMETRY trial is an important step in confirming the benefit to patients observed in our Phase 2b trial and creating a new treatment option for this disease."
"While melanoma has proven resistant to many traditional anti-cancer mechanism categories, we believe this type of cancer, which operates at a particularly high level of oxidative stress, may be especially vulnerable to the mechanism of action of elesclomol," said Eric Jacobson, M.D., chief medical officer, Synta. "Because of the potential of this new approach and because there has never been a phase III trial for a new agent in melanoma that has been preceded by a positive blinded, randomised study for the same agent, we are excited to initiate this trial and have been encouraged by the high level of interest from investigators. With approximately 630 patients and a design mirroring the prior trial, the SYMMETRY trial is highly powered to confirm the results from our phase IIb trial and collect important additional information."
"The positive and constructive discussions with the FDA during the SPA process were important in providing us with clear guidance regarding critical aspects of our trial, and give us confidence the design of the program is suitable to support regulatory approval," added Dr. Jacobson.
The Special Protocol Assessment process provides for a written agreement between the trial's sponsor and the FDA that the design and planned analyses of the clinical trial can be used in support of regulatory approval.
The SYMMETRY trial is enrolling patients with stage IV metastatic melanoma who have not received prior chemotherapy but who may have already been treated with non-chemotherapeutic agents such as biologics. Approximately 630 patients will be enrolled in the blinded, randomised, controlled study, which will be conducted at approximately 150 centres worldwide.
The double-blind, randomised phase IIb clinical trial was conducted in 21 centres in the United States and compared stage IV metastatic melanoma patients treated with elesclomol plus paclitaxel vs. patients treated with paclitaxel alone. In the phase IIb trial, patients who received elesclomol plus paclitaxel showed a doubling of median progression free survival (PFS), the primary endpoint of the study, compared to those patients who received paclitaxel alone. This difference achieved statistical significance. In addition, the percentage of patients in the combination arm that were free of disease progression at six months more than doubled (35 per cent vs. 15 per cent), and the response rate more than tripled (15 per cent vs. 4 per cent).
In June 2007, at the American Society of Clinical Oncology (ASCO) annual meeting, Synta reported additional overall survival results from the phase IIb trial. The analysis of overall survival showed that patients randomised to receive elesclomol plus paclitaxel experienced a median survival of 12 months, compared to 7.8 months for all patients who initially received paclitaxel alone.
Elesclomol was generally well-tolerated in this study; side effects were predictable and were generally comparable to treatment with paclitaxel alone. Neutropenia occurred more commonly in the elesclomol plus paclitaxel group compared to the paclitaxel alone group, but this was manageable and reversible. Although paresthesias occurred more commonly in the elesclomol plus paclitaxel group, the incidence of severe events of this type was low and comparable between groups. The most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhoea, and anaemia.
Melanoma, the most deadly form of skin cancer, arises from melanocytes, the pigment-producing cells of the skin. According to the American Cancer Society, melanoma accounts for approximately five percent of all skin cancers but causes about 75 per cent of all skin cancer-related deaths. An estimated 60,000 people will be diagnosed and nearly 8,200 people will die from melanoma this year in the US alone. If diagnosed and surgically removed while localized in the outermost skin layer, melanoma is potentially curable; however, for patients with metastatic disease, the prognosis is poor, with limited available treatments and an expected survival of only six to nine months. The incidence of melanoma has increased more rapidly than any other cancer during the past ten years. The FDA has not approved a novel, small molecule drug for the treatment of metastatic melanoma in over 30 years.
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercialising small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a diverse pipeline of clinical- and preclinical-stage drug candidates with distinct mechanisms of action and novel chemical structures. All Synta drug candidates were invented by Synta scientists using our compound library and discovery capabilities. Synta has a partnership with GlaxoSmithKline for the joint development and commercialisation of its lead investigational drug candidate, elesclomol, which is in a pivotal phase III clinical trial for the treatment of metastatic melanoma.