The Virtual Window: Clinical Trial Reports--March 2007

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The Clinical Trial Report

â–º PHASE I

BiPar Sciences Recruiting for a Phase 1b Study of BSI-201 Combined With Chemotherapy

On January 4, BiPar Sciences, Inc., announced a phase Ib study of the poly-ADP-ribose polymerase (PARP) inhibitor BSI-201 for the treatment of solid tumors. This study, which is an outgrowth of the ongoing phase I assessment of BSI-201 initiated last year, will study the drug used in combination with various chemotherapeutic agents. The phase I study continues in its goals of confirming the drug’s safety and establishing dosage tolerance. Preclinical studies showed BSI-201’s efficacy in targeted tumor cell death. The drug appears to be effective against a range of tumor types and is well-tolerated by patients.

Thomas F. White, president and CEO of BiPar, reported that, “The knowledge gained from this new combination phase 1b study, from our ongoing monotherapy phase 1 study and from our proprietary genomic data, will lead into a robust BSI-201 phase 2 program.” The three sites participating in the phase Ib study are Philadelphia’s Fox Chase Cancer Center, the Institute for Drug Development (San Antonio), and the Barbara Ann Karmanos Cancer Institute (Detroit).

—Elizabeth Mills

Targepeutics Expects to Begin Clinical Trials of GB13 in 2007

Clinical trials of GB13, a molecular-targeted therapy for cancer, are expected to begin in 2007, according to a January 4 announcement by Targepeutics. The company develops mutated IL-13-based compounds that specifically target the IL-13 cell receptors found on cancer cells but do not bind to normal cell receptors. These mutated compounds are then combined with cellular toxins to create what the company’s website refers to as a “smart bomb” to attack cancer cells. GB13 is one of several such compounds under development.

Unlike existing agents, which affect the IL13Ra1-involving IL-13 binding site, GB13 is specific to IL13Ra2, a biomarker expressed in numerous, including ovarian and prostate cancers. GB13 is composed of genetically engineered mutant of IL-13 combined with PE4E, a derivative of Pseudomonas exotoxin A.

—Elizabeth Mills

Roger Williams Medical Center is Recruiting Patients for a Phase I/II Study of Chemotherapy Followed by Stem Cell Transplantation and Immunotherapy for Stage IIIB or Stage IV Breast and Other Solid Tumors

Roger Williams Medical Center in Providence, Rhode Island, is accepting recruits for a phase I/II study of the efficacy of high-dose chemotherapy followed by peripheral stem cell transplantation and immunotherapy in the treatment of Stage IIIB or Stage IV breast cancer as well as other solid tumors, including kidney, lung, ovarian, and testicular cancers. The study will determine whether the combined treatment modality will allow patients to tolerate higher doses of chemotherapy. Additional objectives are to determine the most effective dosage and mode of administration of chemotherapy, and to assess its side effects.

Participants are grouped according to disease/stage (Stage IIIB or Stage IV breast cancer, solid tumors). Stage IIIB breast cancer patients with chemosensitive tumors are grouped separately from those with chemoresistant tumors; Stage IV breast cancer patients are likewise stratified.

Initial treatment consists of high-dose chemotherapy with either cyclophosphamide IV, thiotepa IV, and carboplatin IV (for chemosensitive tumors), or ifosfamide IV, carboplatin IV, and etoposide IV (for chemoresistant tumors). Chemotherapy is followed by peripheral stem cell transplantation and immunotherapy for nine weeks. Patients receive follow-up at 3 months and

6 months after stem cell transplantation and yearly thereafter.

—Elizabeth Mills

â–º PHASE II

Anti-Cancer Agent PV-10 Received Orphan Drug Designation from FDA

The U.S. Food and Drug Administration (FDA) has given orphan drug status to PV-10, a drug for the treatment of metastatic

melanoma developed by Provectus Pharmaceuticals, Inc. Under the Orphan Drug Act (ODA), Provectus would be entitled to exclusive marketing rights of the drug in the United States for up to seven years if it is the first company to receive marketing approval for the drug. The company is presently conducting a phase I clinical trial of PV-10 at two centers in Australia. Phase II/III studies of PV-10 are expected to begin shortly after the phase I trial is completed.

—Elizabeth Mills

Allos Therapeutics’ Continues Phase II Trial of Pralatrexate, an Agent for Patients With Peripheral T-cell Lymphoma

An independent data monitoring committee (DMC) has recommended continuation of Allos Therapeutics’ phase II trial of pralatrexate (PDX), an agent for the treatment of patients with peripheral T-cell lymphoma (PTCL). The DMC performed a scheduled analysis of safety data from the study and concluded that no major safety concerns exist. Paul L. Berns, president and CEO of Allos, commented that, “This recommendation represents important progress toward the completion of this pivotal study and provides further insight into PDX’s safety profile.”

The phase II, international multicenter study is to determine complete and partial objective response rates, duration of response, and survival both overall and without disease progression. Allos plans to enroll 100 patients who were treated at least once previously and presently have refractory or relapsed PTCL. The trial will consist of a six-week course of once-weekly treatments with 30 mg/m² of PDX followed by one week of rest per treatment cycle. Allos expects the study to be completed by late 2008.

—Elizabeth Mills

â–º PHASE III

Vical Begins Phase III Trial of Allovectin-7® for Metastatic Melanoma

A phase III trial of Allovectin-7® has been announced by Vical Incorporated. The cancer immunotherapy agent will be studied as a first-line treatment for patients with relapsing Stage II or Stage IV metastatic melanoma. As many as 50 sites will participate in the trial, which will be conducted in accordance with a special protocol assessment from the FDA. The FDA has also granted Allovectin-7® orphan drug status due to significant lack of treatment options for invasive and metastatic melanoma.

Vical is moving forward with its phase III trial of Allovectin-7® after successfully concluding a phase II trial in which the drug was evaluated as a single agent for patients with Stage III or IV metastatic melanoma. Allovectin-7® is an MHC-I antigen formed of a plasmid/lipid complex containing the DNA sequences encoding HLA-B7 and beta-2 microglobulin. When injected into tumors, the drug stimulates an immune response against both local and distant metastatic tumors.

The company plans to recruit approximately 375 patients for the study. Eligible participants will have recurrent metastatic melanoma and may have had previous treatment with biotherapy, adjuvant therapy, and/or surgery. Patients who previously received chemotherapy are not eligible for participation. In this randomized trial, approximately 250 patients will be treated with Allovectin-7®, with the remaining patients to receive either dacarbazine or temozolomide, according to their physician’s preference. The primary objective of the study is to compare objective response rates at six months or more after randomization; additional goals include evaluation of the agent’s safety and tolerability, as well as survival rates.

—Elizabeth Mills

Poniard Announces Phase III Trial of Picoplatin for Small Cell Lung Cancer

A phase III trial of Picoplatin for the treatment of small-cell lung cancer (SCLC) will begin early this year, according to Poniard Pharmaceuticals, Inc. The new generation agent was designed to prevent or alleviate platinum resistance associated with chemotherapy for solid tumors.

Approximately 400 patients will be recruited for the projected 20-month study. Participants will include patients whose disease did not respond to treatment with cisplatin or carboplatin as well as those who are presently within six months of completing a course of chemotherapy. Randomization will be 2:1, comparing treatment with picoplatin plus best supportive care to best supportive care alone. The goals of the trial are to evaluate patient response rates, improvement in management of diseaserelated symptoms, and survival (both overall and without progression).

—Elizabeth Mills

The Unsuccessful Completion of YM BioScience’s Phase III Trial of Breast Cancer DrugSignificantly Impacts Stock Price

An independent review committee has determined that the Phase III trial of YM BioScience’s breast cancer drug, tesmilifene,

in combination with epirubicin and/or cyclophosphamide, is not likely to yield significant benefits. The drug is still being evaluated in phase II trials in combination with other drugs and has recently completed a phase III trial for breast cancer in combination with doxorubicin. The news of the halt caused YM BioScience’s stock to drop to $1.77 per share.

The trial was designed to test tesmilifene in patients with recurrent or metastatic breast cancer in combination with epirubicin and/or cyclophosphamide. Tesmilifene is a small molecule that is designed to selectively target multiple-drug

resistant tumor cells, making them more susceptible to chemotherapy. The phase III trial was halted after it was reviewed

by an independent Data Safety Monitoring Board (DSMB). News of the termination of the trial resulted in an almost-50% drop in share prices. Trading ended January 30 with YM bioscience’s shares at $3.72 and started trading at $1.77 on reopening January 31.

The trial successfully enrolled more than 700 women with recurrent or metastatic cancer by September of 2005. The study had also been granted fast track status by the FDA. The review was a safety and efficacy analysis that had been planned to take place periodically throughout the trial. The endpoint of the trial was to be determined by two possible outcomes of the review board, either determination that tesmilifene showed statistical significance in improving overall survival or if it was determined that such evidence would not be found.

After analyzing the data for safety and efficacy, the DSMB recommended that the trial be halted based on the results of their analysis. The DSMB analyzed 351 events in the trial and came to the conclusion that tesmilifene was not going to provide a significant difference in overall survival compared to the control, epirubicinand/or cyclophosphamide without tesmilifene.

“We are very disappointed by this outcome and will be evaluating the data to understand why tesmilifene did not add a clinical benefit in this trial,” said David Allan, chairman and CEO of YM BioScience. “Upon completing the review of the phase III data, the company will consider its options relating to tesmilifene.” Currently, tesmilifene is in four other phase II clinical trials. The other trials include one for evaluating the drug with docetaxel in patients with metastatic breast cancer. The other three trials are

testing tesmilifene in combination with other therapies in hormone-refractory prostate cancer. Tesmilifene has also completed

a phase III trial with doxorubicin in metastatic or recurrent breast cancer.

—Nick Rose