Abraxis BioScience presents phase 3 trial data on metastatic malignant melanoma

Abraxis BioScience, Inc. (NASDAQ:ABII) presented trial design information from its ongoing phase 3 registration trial of nanoparticle albumin bound (nab^®) driven chemotherapy, nab-paclitaxel (ABRAXANE^® for Injectable Suspension; paclitaxel albumin protein-bound particles for injectable suspension), in melanoma, an aggressive form of skin cancer that affects more than 68,000 people in the U.S. each year. Melanoma is the leading cause of skin cancer death in the United States, killing more than 8,000 people annually.

“As the body of evidence continues to build it validates our commitment to interrogating the activity of ABRAXANE in difficult-to-treat tumor types such as metastatic melanoma”

Abraxis BioScience also presented an abstract describing the design of its ongoing phase 3 registrational trial of nab-paclitaxel for the treatment of metastatic malignant melanoma (MMM). The pivotal phase 3 clinical trial program exploring the use of nab-paclitaxel (150 mg/m) in advanced melanoma was discussed during the "Trials in Progress" session at the 46^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

New data on Abraxis BioScience's novel nab technology, which leverages albumin nanoparticles for the active and targeted delivery of chemotherapeutics to the tumor, has been presented at ASCO in a wide range of tumor types, including pancreatic, ovarian, breast, head and neck, and non-small cell lung cancers. The company is investigating the potential of nab-driven chemotherapy to deliver cytotoxic agents directly to the tumor microenvironment through a previously unrecognized tumor-activated, albumin-specific biologic pathway in the most difficult-to-treat cancer types, including metastatic malignant melanoma.

"As the body of evidence continues to build it validates our commitment to interrogating the activity of ABRAXANE in difficult-to-treat tumor types such as metastatic melanoma," said Patrick Soon-Shiong, M.D., Executive Chairman and Founder of Abraxis BioScience.

Currently approved for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy, ABRAXANE has also been granted orphan drug designation by the Food and Drug Administration for the treatment of stage IIB-IV melanoma as well as pancreatic cancer.

About the Studies

I. An open-label, multicenter, phase 3 trial of nab-paclitaxel (NP) vs dacarbazine (DTIC) in previously untreated patients (PTs) with metastatic malignant melanoma (MMM) (Abstract #TPS314)

In this ongoing phase 3 registration trial, cytotoxic chemotherapy-naïve patients with metastatic malignant melanoma are randomized into two treatment arms consisting of either nab-paclitaxel (150 mg/m²) on days 1, 8, and 15 every 4 weeks or dacarbazine (1000 mg/m²) on day 1 every 21 days. The primary efficacy endpoint is progression-free survival (PFS) and the main secondary endpoint is overall survival (OS). Other secondary endpoints include safety and tolerability of the regimens, nab-paclitaxel pharmacokinetic parameters, effects of therapy on and the relationship of response to the levels of SPARC and gene methylation, mutational and other biomarkers, response rate, stable disease rate at greater than or equal to 16 weeks and duration of response. Dosage reductions of nab-paclitaxel to 120 and 90 mg/m² and of dacarbazine to 800 and 600 mg/m² and the use of filgrastim for neutropenic fever are allowed. Efficacy is assessed by CT scans every eight weeks in both arms. The study accrual goal is 514 patients, randomized to 257 patients per treatment arm. A total of 104 multinational sites are anticipated. Currently 34 sites are open and accrual is on schedule with 135 patients enrolled. .

II. Tumor SPARC microenvironment signature (SMS) and plasma levels in a phase II trial of unresectable stage IV melanoma treated with nab-paclitaxel and carboplatin: a translational study of NCCTG trial N057E (Abstract #8578)

In this Phase II study, 76 patients with unresectable stage IV melanoma who were either chemotherapy naïve or pretreated were given therapy. The treatment regimen consisted of nab-paclitaxel (100 mg/m²) and carboplatin (AUC 2) on days 1, 8 and 15 of a 28-day cycle until disease progression. SPARC in tumor biopsies was measured using a validated SPARC IHC. The primary objective was to use the developed SMS to distinguish between low risk and high risk groups with respect to PFS and OS. Tumor SPARC IHC data was available for 40 patients, suggesting that SPARC in the tumor microenvironment may play an important role in the outcome of melanoma patients:

• A unique SPARC signature was developed for melanoma patients to distinguish early progressers (LR,>
• Plasma SPARC levels were higher in melanoma patients than normal controls (mean 300 ng/ml,>
• For the high-risk versus low-risk groups respectively, median PFS increased from 3.7 to 6.6 months and median OS increased from 9.4 to 17.7 months

III. Oblimersen one-hour IV infusion in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma (Abstract #8561)

In this ongoing Phase 2 study, 13 chemotherapy-naïve advanced melanoma patients with an ECOG PS of 0-2 and baseline LDH greater than or equal to 1.1 x ULN have been treated. Therapy consisted of a 30-minute IV infusion of nab-paclitaxel (175 mg/m²) (days 4, 25), oral temozolomide (75 mg/m²) (days 1-42) and a 1-hour IV infusion of oblimersen (900 mg) (days 1, 4, 8, 11, 22, 25, 29, 32) on a 56-day cycle. The primary endpoint for this study is safety and efficacy, with responses evaluated based on RECIST criteria. Results included:

• Three patients who progressed after one cycle
• Ten patients who are continuing treatment; one has demonstrated complete response, four have demonstrated partial response (PR), four have stable disease (SD), and one has yet to be evaluated for response
• One patient with a PR demonstrated increased intra-tumoral caspase 3 and decreased Bcl-2 on day 4 due to an overall reduction in tumor burden, which correlated with a decrease in shed collagen epitopes and clinical response

Non-hematological toxicities were generally mild with one patient hospitalized for drainage of a pre-existing pleural effusion (grade 3), for which she had declined treatment prior to enrollment. No other Grade 3 or 4 events have occurred. Planned enrollment of 14 patients is continuing.

The results from these studies have not been formally reviewed by the Food and Drug Administration.