By Brady Huggett

Onyx Pharmaceuticals Inc. reported preliminary Phase II trial results of its lead product, CI-1042 (ONYX-015) for premalignant oral dysplasia, administered to patients as a mouthwash, at the 37th Annual Meeting of the American Society of Clinical Oncology in San Francisco.

Researchers presented data showing CI-1042 was well tolerated and may cause resolution of dysplasia in some patients. The product was administered at a weekly dose of 1,010 particles for 12 weeks. Patients that demonstrated histologic improvement were eligible to receive another 12 weeks of treatment.

Of the 10 patients involved, resolution of evident dysplasia was observed in two patients, and improvement in the histologic grade of dysplasia was shown in four patients. Three patients had progression to disease despite therapy, and one patient had initial improvement followed by progression. No significant clinical toxicity was observed.

CI-1042 is a tumor-selective, modified adenovirus that has been genetically engineered to replicate in and kill cancer cells that have dysfunctional p53. The product is jointly developed by Onyx and Pfizer Inc., of New York.

In other news from ASCO:

¿ AEterna Laboratories Inc., of Quebec City, Quebec, said patient recruitment in its Phase III trial of Neovastat in renal cell carcinoma is more than half complete. The 280-patient study aims to evaluate the efficacy of Neovastat, an anti-angiogenic compound, in prolonging survival.

¿ AnorMED Inc., of Vancouver, British Columbia, presented data on its platinum-based anticancer agent, ZD0473. Preliminary data from a Phase II monotherapy trial of ZD0473 in the second-line treatment of ovarian and small-cell lung cancer showed the compound produced objective responses in both platinum therapy-sensitive and -resistant patients, the company said. Responses to ZD0473 also were seen among patients with small-cell lung cancer who had relapsed after initial chemotherapy. No evidence of clinically significant neurotoxicity or nephrotoxicity was observed.

¿ Aphton Corp., of Miami, presented interim results from a Phase II trial in patients with metastatic stomach cancer, results from trials with colorectal and pancreatic cancer patients and studies and preclinical trials. In the Phase II trial of Aphton¿s anti-gastrin 17 immunogen, given with cisplatin and 5-FU, two of the six evaluable patients had tumor volume shrinkage of more than 50 percent. Three had tumor volume shrinkage of less than 50 percent, and one patient had complete disappearance of six liver metastases.

¿ Aronex Pharmaceuticals Inc., of The Woodlands, Texas, reported data from a Phase I trial of Annamycin for the treatment of patients with acute myeloid and lymphoid leukemia who had relapsed or were refractory to current therapies. Of the 21 patients enrolled, two achieved complete remission. Physicians reported that Annamycin was generally well tolerated with no observed cardiotoxicity.

¿ Cell Genesys Inc., of Foster City, Calif., presented data on Phase II trials of its prostate cancer product, GVAX. One trial examined 55 patients who had failed hormone therapy and showed a trend toward increased median time to progression measured by both bone scan and prostate-specific antigen (PSA) in patients receiving a higher dose of the vaccine compared to a lower dose. The median time to clinical progression achieved with the higher dose was comparable to that seen with standard chemotherapy. In a second trial in 41 early stage prostate cancer patients with increasing PSA measurements following surgery, the median time to progression had not been reached and patient follow-up is continuing.

¿ EntreMed Inc., of Rockville, Md., presented completed Phase I trials of rhEndostatin, an angiogenesis inhibitor. It was tested in several types of tumors in patients no longer responding to conventional therapy. The product showed no serious side effects, and EntreMed plans to move it into Phase II trials.

¿ Genaera Corp., of Plymouth Meeting, Pa., presented Phase IIa trial data in non-small-cell lung cancer patients for its anti-angiogenic drug, squalamine. The data included an objective response seen in 29 percent of patients (nine of 31) receiving the treatment dose of squalamine (300 mg/m2/day) for one or more cycles of therapy. Overall, 27 percent of all patients (12 of 45) at all doses experienced an objective response. The historical response rate for this group of patients treated with carboplatin and paclitaxel alone is 15 percent. Also, Genaera announced data from its ongoing multicenter Phase II trial in recurrent and resistant advanced ovarian cancer.

¿ Genentech Inc., of South San Francisco, reported preliminary results from a Phase II trial of Rituxan (rituximab) and fludarabine in previously untreated patients with chronic lymphocytic leukemia and a study evaluating Rituxan alone as a front-line and maintenance therapy for patients with low-grade non-Hodgkin¿s lymphoma or small lymphocytic leukemia. In the Phase II study, there was an overall response rate of 90 percent and a 47 percent complete response rate in the study arm that received fludarabine with Rituxan. In the front-line study, 28 of 60 evaluable patients (47 percent) had an objective response, with 7 percent achieving complete responses. Twenty-nine patients had stable or minor responses.

¿ Immunex Corp., of Seattle, and Abgenix Inc., of Fremont, Calif., presented preliminary results from a Phase I trial of ABX-EGF, their fully human monoclonal antibody in development against cancers expressing the epidermal growth factor receptor. The product appeared to be well tolerated at tested doses in the ongoing trial, and the companies initiated a Phase II study in kidney cancer.

¿ Introgen Therapeutics Inc., of Austin, Texas, reported results of a Phase II lung cancer study and a Phase I ovarian cancer study of INGN 201. In the lung cancer study, patients were given INGN 201 in combination with radiation therapy. Twelve of the 19 patients (63 percent) had complete or partial responses at the injected site measured three months after completing the treatment. Four patients could not be evaluated. Historically, the response rate in locally advanced lung cancer following radiotherapy given alone is 18 percent. In the second study, 10 women with refractory ovarian cancer were treated monthly with three doses of INGN 201 delivered intraperitoneally. Results showed up to a 17-fold increase in the percent of tumor cells expressing p53 protein.

¿ Ligand Pharmaceuticals Inc., of San Diego, presented results of a multicenter Phase I/II study of Targretin capsules in combination with interferon alfa-2b (Intron A) in patients with advanced renal cell cancer. The optimal dose was found to be 400 mg/m2/day. In Phase II, 31 patients were assigned to a lower-risk group and 16 to a higher-risk group and given 400 mg/m2/day Targretin capsules. The overall response rate for this group was 8.5 percent. Median survival by Kaplan-Meier analysis for patients receiving 400 mg/m2/day was 16 months. One-, two- and three-year survivals by life-table analysis were 64 percent, 34 percent and 20 percent, respectively. Clinical studies with Intron A alone show a median survival of one year.

¿ Matrix Pharmaceutical Inc., of Fremont, Calif., presented data on its product IntraDose Injectable Gel, for the treatment of solid tumors, from two Phase III studies in patients with squamous cell carcinoma of the head and neck. In the double-blinded, placebo-controlled trials, patients with advanced recurrent or refractory head and neck squamous cell carcinoma were randomized to receive IntraDose or placebo gel by direct intratumoral injection. Study endpoints included objective tumor response and patient benefit as measured by the treatment goals questionnaire. Time to initial response ranged from seven to 162 days, with a median of 21 days. The combined trial results showed a response rate of 29 percent (19 percent complete and 10 percent partial) in IntraDose-treated patients ¿ greater than patients receiving placebo.

¿ Peregrine Pharmaceuticals Inc., of Tustin, Calif., reported preliminary efficacy and safety results from a Phase II brain cancer trial using Cotara, its tumor necrosis drug. The primary objective of the study was to determine the median time to progression of treated patients compared with a historical control population. The overall median time to progression was 13.9 weeks. The median time to progression for the historical control population was eight weeks.

¿ Therion Biologics Corp., of Cambridge, Mass., reported on its products, vaccinia-CEA and Alvac-CEA, developed in collaboration with the National Cancer Institute, of Bethesda, Md., and Aventis Pasteur SA, of Lyon, France, in a Phase I/II trial with patients with late-stage metastatic cancers. Five of nine patients treated with sequential vaccinations of the two products showed increased immune response and also remained alive two years out compared to zero long-term survivors in other treatment groups.

¿ Vion Pharmaceuticals Inc., of New Haven, Conn., reported results of a Phase I trial of Triapine, showing that continuous infusion, given over 96 hours every three weeks to patients with advanced and treatment-resistant cancer, was generally well tolerated and showed evidence of antitumor activity. Triapine is an inhibitor of the enzyme ribonecleotide reductase.

¿ Wilex AG, of Munich, Germany, and the Ludwig Institute for Cancer Research presented results from a Phase I trial of unconjugated WX-G250 in 12 renal cell carcinoma patients. The trials showed WX-G250 to be safe and well tolerated. Patients received repeated weekly doses of up to 50 mg/m2 for more than six weeks. At the end of the first six-week cycle in the trial, eight patients had stable disease and one had complete response of a single lung metastasis.

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