The California-based Hana Biosciences, a biopharmaceutical company focused on strengthening the foundation of cancer care, said it commenced dosing of Marqibo (vincristine sulfate injection, Optisome) in the phase II clinical trial. The company revealed that it has dosed the first two patients in the Marqibo trial for the treatment of metastatic malignant uveal melanoma.
The primary objective of Hana's phase II study is to assess the efficacy of Marqibo as determined by response rates in patients with metastatic malignant uveal melanoma. Secondary objectives are to assess the safety and antitumour activity of Marqibo as determined by response duration, time to progression, and overall survival. The patient population is defined as adults with uveal melanoma and confirmed metastatic disease that is untreated or that has progressed following one prior therapy. Hana expects to enrol up to 30 patients in this clinical trial, which is being conducted at the University of Texas MD Anderson Cancer Center.
The phase II clinical trial is supported by data from a Phase 1 trial of Marqibo in patients with metastatic melanoma originating in the eye demonstrating promising single-agent activity. This data was reported earlier this year at the 43rd American Society of Clinical Oncology (ASCO) Annual Meeting.
In the phase I study, an objective response rate (complete response plus partial response) of 13 per cent and stable disease rate of 20 per cent was achieved among 15 patients with histologically confirmed, surgically non-resectable metastatic cutaneous, mucosal, or uveal melanoma. One of four subjects with uveal melanoma metastatic to the lung achieved a complete response. Marqibo was generally well tolerated and showed promising single agent activity against metastatic melanoma.
"Patients with metastatic uveal melanoma generally do not respond to systemic chemotherapy and have limited treatment options. We are encouraged by the results we have seen to date with Marqibo and believe that it will benefit this patient population," said Agop Y. Bedikian, M.D., Professor, Melanoma Medical Oncology Department at the University of Texas MD Anderson Cancer Centre in Houston and the principal investigator for the trial.
"We are excited to initiate this phase II trial based on clinical data that suggest that Marqibo has promising activity in melanoma, in addition to its potential in treating hematologic malignancies," stated Steven R. Deitcher, M.D., president and CEO, Hana Biosciences. "We are delighted to collaborate with world-renowned oncology experts like Dr. Bedikian and his team at MD Anderson Cancer Center to explore the potential of our novel therapeutics to improve treatment outcomes for patients with difficult-to-treat cancers."
Uveal melanoma is a relatively rare cancer of the coloured part of the eye and the surrounding areas, called the uvea. Uveal melanoma is the most common primary intraocular malignant tumour in adults and represents five to six percent of all melanoma diagnoses. The incidence of uveal melanoma is reported to be 3,500-4,000 per year. Metastasis is via vascular spread, and approximately 40-50 percent of patients with primary uveal melanoma will ultimately develop metastases. At the time of diagnosis, over 95 per cent of patients have disease limited to the eye, but at least 30 per cent of these patients will die of systemic metastases at five years and 45 per cent at 15 years. The liver is involved in up to 90 percent of individuals who develop metastatic disease. In general, metastatic uveal melanoma is unresponsive to systemic chemotherapy.
Marqibo, a novel, targeted, Optisomal formulation of vincristine, has shown promising anti-cancer activity in patients with acute lymphoblastic leukaemia (ALL), non-Hodgkin's lymphoma, and melanoma in several clinical trials. Vincristine is FDA-approved as a single agent and in combination regimens for the treatment of hematologic malignancies such as lymphomas and leukaemia's. Vincristine, a microtubule inhibitor, kills cancer cells when they enter a very specific point in the cell cycle, and its efficacy is concentration- and exposure duration-dependent. Marqibo is believed to extend the circulation time of vincristine in the bloodstream, increase targeting of the drug to malignant cells, and enhance exposure duration at the site of the disease. Unlike regular vincristine, Marqibo is dosed based on patient body surface area without the need to limit the dose to avoid neurotoxiciites.
Optisomes are a new generation of unique, sphingomyelin/cholesterol-based nanoparticles designed to encapsulate cell cycle-specific chemotherapeutics designed for improved efficacy with reduced toxicity. Optisomes are approximately 100 nanometers in diameter and able to encapsulate and transport cancer drugs preferentially to tumour sites. While too large to easily migrate out of normal blood vessels, Optisomes are able to migrate across the more "leaky" vasculature of a tumour, resulting in higher concentrations of drugs at tumour sites than in normal tissue. Optisomes' unique sphingomyelin-cholesterol composition is particularly well suited to cell cycle-specific agents such as vincristine, vinorelbine and topotecan. The relative rigidity of the Optisomes' outer shell results in a long circulating half-life and sustained drug release at the tumour site, which may increase tumour cell exposure during the most vulnerable phases of cell division. Combined, these factors are key to the Optisome advantage as sustained drug exposure increases tumour cell death. Hana's Optisome pipeline includes Marqibo (vincristine), Alocrest (vinorelbine) and Brakiva (topotecan).
Hana Biosciences, Inc. is a, California-based biopharmaceutical company focused on acquiring, developing, and commercialising innovative products to strengthen the foundation of cancer care. The company is committed to creating value by building a best in-class team, accelerating the development of lead product candidates, expanding its pipeline by being the alliance partner of choice, and nurturing a unique company culture.