Assistant Managing Editor

As the industry prepared for the first deluge of American Society of Clinical Oncology (ASCO) data Thursday night, cancer drug company Allos Therapeutics Inc. managed to capture a little attention of its own early in the day by reporting promising interim data from its pivotal Phase II study of PDX (pralatrexate) in peripheral T-cell lymphoma (PTCL).

An early peek at results from the first 65 evaluable patients in the PROPEL (Pralatrexate in patients with Relapsed Or refractory PEripheral T-cell Lymphoma) trial showed that 29 percent, or 19 patients, experienced either a complete or partial response when treated with PDX, a dihydrofolate reductase inhibitor, as determined by a central independent oncology review. Subjects in the single-arm, open-label study are receiving 30 mg/m2 of PDX once weekly for six weeks followed by one week of rest per cycle, plus supplemental treatment with vitamin B12 and folic acid. However, patients were considered evaluable if they received at least one dose of PDX and had a confirmed diagnosis of PTCL.

Executives of Westminster, Colo.-based Allos said they were "pleased" with those interim data, and expect to release top-line data from the full 100-patient study by the end of this year. The trial is being conducted under a special protocol assessment with the FDA, and pending positive results, the company will file a new drug application "as expeditiously as possible," Paul Berns, president and CEO, said during a conference call.

The company launched the pivotal trial in August 2006, shortly after reporting stellar interim data from an earlier Phase I/II study showing that four of seven evaluable patients who had failed multiple prior therapies achieved a complete response following treatment with PDX. Full data from that trial are being prepared for publication, but Chief Medical Officer Pablo Cagnoni told analysts and investors during the call that results showed a response rate of 54 percent among patients who completed at least one full cycle of treatment. (See BioWorld Today, Aug. 3, 2006.)

Allos has not disclosed a specific response rate needed for PDX approval in PTCL, though, based on drugs approved for other hematological malignancies, PDX likely will need to show at least a 20 percent response rate to gain an FDA nod.

Cambridge, Mass.-based Genzyme Corp.'s Clolar (clofarabine) was approved in 2004 in pediatric relapsed or refractory lymphoblastic leukemia based on a 20 percent response rate, and in 2005, London-based GlaxoSmithKline plc gained approval of Arranon (nelarabine) in adults and children with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma based on a data showing a response rate of 22 percent.

As its secondary endpoints, the PROPEL trial is evaluating duration of response, progression-free survival and overall survival.

At the time the interim data were collected, median duration of response was not able to be estimated. The most common treatment-related Grade 3 and Grade 4 adverse events were mucositis, which was observed in 14 percent of patients, and thrombocytopenia, observed in 24 percent.

PDX, which has both orphan and fast-track status in the U.S., has the "potential to offer a new treatment option for this challenging disease," Cagnoni said.

PTCLs comprise a group of rare blood cancers that account for about 10 percent to 15 percent of all non-Hodgkin's lymphoma cases. There are an estimated 6,700 PTCL patients in the U.S., but no therapies have been approved specifically to treat the disease. Most PTCL patients are treated with the CHOP regimen - cyclophosphamide, doxorubicin, vincristine and prednisone - but its effects are limited.

In addition to Allos, several other firms are advancing drugs for PTCL, including Copenhagen, Denmark-based TopoTarget A/S, which acquired full rights to histone deacetylase (HDAC) inhibitor belinostat from partner CuraGen Corp., of Branford, Conn., in April and plans to move into a pivotal Phase III program in the second half of this year. Gloucester Pharmaceuticals Inc., of Cambridge, Mass., also has an HDAC inhibitor, romidepsin, which is in Phase II testing in PTCL. (See BioWorld Today, April 23, 2008.)

Ziopharm Oncology Inc., of Bethesda, Md., has darinaparsin, an organic arsenic compound that is in Phase II testing in several hematological malignancies, including PTCL, and Thousand Oaks, Calif.-based Amgen Inc. recently picked up rights to a Phase I-stage antibody compound targeting CCR4 from Japanese firm Kyowa Hakko Kogyo Co. Ltd. (See BioWorld Today, March 7, 2008.)

Beyond PTCL, Allos also is testing PDX in five other studies, including a Phase IIb trial initiated in January to test PDX against Tarceva (erlotinib, Genentech Inc. and OSI Pharmaceuticals Inc.) in patients with Stage IIIb/IV non-small-cell lung cancer who have failed treatment with at least one prior platinum-based chemotherapy regimen.

Other studies are ongoing in non-Hodgkin's lymphoma (B cell), non-Hodgkin's lymphoma in combination with gemcitabine and cutaneous T-cell lymphoma.

PDX is "rationally designed for improved uptake and retention in malignant cells," Berns said, "so we believe it has potential in a number" of hematological and solid tumors.

Shares of Allos (NASDAQ:ALTH) lost 5 cents Thursday to close at $5.87.