Allos Therapeutics Inc., a biopharmaceutical company committed to the development and commercialization of innovative anti-cancer therapeutics,  has released interim results from its ongoing phase I combination study of Folotyn (pralatrexate injection) and Bexarotene to demonstrate the activities in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL).

The combination treatments demonstrated encouraging activity in heavily pre-treated patients (median of 3 prior systemic regimens). Data were presented during an oral presentation at the Fourth Annual T-cell Lymphoma Forum, on January 28 in San Francisco, California.

Of the 14 patients treated to date, response data were available for 10 patients and 4 patients have not yet reached their first response assessment. Overall, 6 out of 10 patients achieved a response, including one complete response and 5 partial responses. At the maximum tolerated dose, 4 of 7 patients achieved a response, including one complete response and 3 partial responses. Interim data indicates that the combination regimen has been reasonably well tolerated. The most common adverse events (AE) among the 4 patients with AE data available were dizziness, dyspnea, myalgia, mucosal inflammation, and pyorexia (n=2 each).

“We are encouraged by the response rates and tolerability observed at the maximum tolerated dose of the combination folotyn plus bexarotene in heavily pre-treated patients with relapsed or refractory CTCL,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics. “We look forward to completing patient enrollment of the expanded cohort in order to further inform the design of a planned phase III registration study.”

CTCL is a group of T-cell non-Hodgkin lymphomas. In its early stages, CTCL primarily affects the skin, causing patches, plaques, and tumours, as well as redness and itching; however, as it progresses, CTCL can spread to the blood, lymph nodes, and internal organs. For some patients, their disease will progress despite treatment with topical and skin directed therapies and will require systemic treatments, including chemotherapies. Even when CTCL is found in an early stage, it can be difficult to treat and usually returns after initial treatment.

This ongoing, open label, multi-centre, dose-finding, phase I study is evaluating the combination of Folotyn and bexarotene in patients with relapsed or refractory CTCL who received at least one prior systemic therapy. The first phase of the study employed a standard dose-escalation design to determine the maximum tolerated dose (MTD). The maximum tolerated dose has been determined to be 15 mg/m2 of weekly Folotyn and 150 mg/m2 of daily bexarotene. The cohort determined to be the optimal dose/schedule is currently at 14 patients and is being expanded to evaluate Folotyn and bexarotene in a total of 30 patients at the MTD.

Folotyn, a folate analogue metabolic inhibitor, was discovered by Sloan-Kettering Institute for Cancer Research, SRI International and Southern Research Institute and developed by Allos Therapeutics. In May 2011, the Company entered into a strategic collaboration agreement with Mundipharma International Corporation Limited (Mundipharma) to co-develop Folotyn globally. Under the agreement, Allos retains full commercialization rights for Folotyn in the United States and Canada, with Mundipharma having exclusive rights to commercialize Folotyn in all other countries.

In September 2009, the US Food and Drug Administration (FDA) has granted accelerated approval for Folotyn for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. Folotyn has been available to patients in the US since October 2009.

CTCL is comprised of indolent non-Hodgkin T-cell lymphomas which have their primary manifestations in the skin. The most common CTCL subtypes are mycosis fungoides and Sézary syndrome. The incidence of CTCL is increasing in the United States with approximately 3,000 new cases being diagnosed annually. CTCL affects over 30,000 in the US and Canada.