Prometheus Laboratories Inc. Launches PROCLIVITY(SM) 01 Clinical Trial of Proleukin® (Aldesleukin for Injection) Plus Vemurafenib Therapy in Patients with Metastatic Melanoma

SAN DIEGO, May 9, 2013 /PRNewswire/ -- Prometheus Laboratories Inc., a specialty pharmaceutical and diagnostic company, announces that PROCLIVITY 01, a multi-center study of Proleukin^® (High Dose Interleukin-2 (HD IL-2))[1] plus vemurafenib therapy in patients with BRAF ^V600 mutation-positive metastatic melanoma (mM) is enrolling patients. HD IL-2 therapy is administered in specialized hospitals as inpatient therapy and vemurafenib is an oral outpatient therapy.  The Phase IV study is currently open in 12 sites and will be conducted in approximately 25 sites in the United States.

"Metastatic melanoma is a rapidly progressing cancer for which approved systemic therapy has been limited until the past 2 years," stated James Lowder, MD, Senior Director of Oncology Clinical Development and Medical Affairs at Prometheus. "Immune-based therapy with the FDA-approved HD IL-2 has long been shown to produce meaningful and durable responses in a small percentage of patients with metastatic melanoma.[2] The recently FDA-approved vemurafinib produces rapid, but temporary, reductions in tumor size in a majority of patients with an activating mutation of the BRAF signaling protein. The rationale for the PROCLIVITY 01 trial is based on data suggesting that the activity of vemurafenib and IL-2 is potentially synergistic."[3]

The open-label, two-arm study is enrolling mM patients with BRAF^V600 oncogene mutations. Patients will initially receive treatment with vemurafenib sequenced with two courses of HD IL-2.  Cohort one, on which the study's statistics are based, will consist of 135 patients naive to vemurafenib and HD IL-2 therapy. These patients will be initially treated with 6 weeks of vemurafenib alone followed by two courses of HD IL-2 sequenced with continued vemurafenib. Cohort two patients will have received 7-18 weeks of vemurafenib prior to adding HD IL-2 and can be enrolled after starting vemurafenib.  The second cohort will explore the effect of more prolonged vemurafenib treatment on adverse events and efficacy. 

"The importance of BRAF mutations in melanoma and the continuing increase in FDA approved agents with different mechanisms makes clinical trials studying the sequential administration of several agents vital," said melanoma patient Stan Adler. "Combining immunotherapy with targeted therapy may both improve outcomes and personalize care for patients with metastatic melanoma."

The study's primary endpoint is complete response (CR) at 26 weeks (+/-3 weeks) from the start of HD IL-2.  Patient assessment of overall response rate (OSS), progression-free survival (PFS) and overall survival (OS) will be followed in the PROCLAIM^SM registry study.

According to the American Cancer Society, an estimated 9,480 Americans will die of metastatic melanoma in 2013.[4] HD IL-2 is used to treat the disease and produces complete and partial responses in 16% of patients, many of which are durable for years.[1] "The past decade has been marked by significant advances in understanding the key molecular signaling events underlying the pathogenesis of melanoma," explained Dr. Lowder. "We now know that the BRAF ^V600 mutation is found in approximately 50% of melanomas, especially in younger individuals.[3] If, by combining BRAF inhibition with immunotherapy, we could improve the durable complete response rate over that seen with high-dose interleukin-2 alone, it would be viewed as a significant advance in the management of metastatic melanoma."

About Proleukin

Proleukin (aldesleukin) for injection is a recombinant human interleukin-2 for treatment in adults with metastatic melanoma and metastatic kidney cancer (mRCC). Proleukin therapy is a form of immunotherapy that enhances the body's natural immune system to help fight these types of cancer. Proleukin has been used for over 15 years in the treatment of metastatic melanoma and over 20 years in the treatment of metastatic kidney cancer (renal cell carcinoma). Complete plus partial response rates were 15% in mRCC patients and 16% in mM patients.

Important Safety Information

Therapy with Proleukin (aldesleukin) should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress testing and formal pulmonary function testing. Extreme caution should be used in patients with a normal thallium stress test and a normal pulmonary function test who have a history of cardiac or pulmonary disease.

Proleukin should be administered in a hospital setting under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available.

Proleukin administration has been associated with capillary leak syndrome (CLS), which is characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space. CLS results in hypotension and reduced organ perfusion, which may be severe and can result in death. CLS may be associated with cardiac arrhythmias (supraventricular and ventricular), angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes.

Proleukin treatment is associated with impaired neutrophil function (reduced chemotaxis) and with an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Consequently, preexisting bacterial infections should be adequately treated prior to initiation of Proleukin therapy. Patients with indwelling central lines are particularly at risk for infection with gram-positive microorganisms. Antibiotic prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin has been associated with a reduced incidence of staphylococcal infections. Proleukin administration should be withheld in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma.

About Interleukin-2

Interleukin-2 (IL-2) is a cytokine protein that occurs naturally in the body and plays an important role in activating the immune system. Proleukin is a recombinant version of IL-2.  Proleukin possesses the same properties as naturally occurring IL-2 and when administered to patients with mM and mRCC activates the immune system to recognize and eliminate cancer cells.

Please see full Prescribing Information for Proleukin.

About Prometheus

Prometheus Laboratories Inc. is committed to improving lives through the development and commercialization of novel pharmaceutical and diagnostic products that enable physicians to provide greater individualized patient care. Prometheus is a leader in applying the principles of personalized medicine to the diagnosis and treatment of gastrointestinal diseases and is applying these principles to oncology. Its strategy includes the marketing and delivery of pharmaceutical products complemented by proprietary diagnostic testing services. By integrating therapeutics and diagnostics, Prometheus believes it can provide physicians with more targeted solutions to optimize care for their patients. Prometheus became part of Nestle Health Science in July 2011. The corporate offices of Prometheus are located in San Diego, California. For more information about Prometheus, please visit www.prometheuslabs.com.

About Nestle Health Science

Nestle Health Science, a wholly-owned subsidiary of Nestle, intends to spearhead the development of science-based personalised nutritional solutions. Building on its core HealthCare Nutrition business, the company has ambitions to address chronic conditions in the area of Gastrointestinal Health, Metabolic Health and Brain Health. Nestle Health Science offers nutritional solutions for people with specific dietary needs related to illnesses, disease states or the special challenges of different life stages. Nestle Health Science employs around 3,000 people worldwide and has its headquarters in Lutry, Switzerland. For more information, please visit www.nestlehealthscience.com.

[1] PROLEUKIN Prescribing information.  600,000 International Units/kg (0.037 mg/kg) dose administered every 8 hours by a 15-minute intravenous infusion for a maximum of 14 doses. Following 9 days of rest, the schedule is repeated for another 14 doses, for a maximum of 28 doses per course, as tolerated. Page 15 (http://www.proleukin.com/assets/proleukin.pdf)

[2] Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17:2105-16.

[3] Frederick DT, Piris A, Cogdill AP, et al. BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma. Clinical Cancer Research Published OnlineFirst January 10, 2013.

[4] American Cancer Society. Cancer Facts & Figures 2013. Atlanta, GA: American Cancer Society; 2013.

Proleukin is a registered trademark of Novartis Vaccines and Diagnostics, Emeryville, CA

PROCLIVITY,PROCLAIM, PROMETHEUS and the link design are trademarks or registered trademarks of Societe des Produits Nestle, Vevey, Switzerland.

SOURCE Prometheus Laboratories Inc.

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