Mary Welch

Onyx Pharmaceuticals Inc. reported that nine of 10 head and neck cancer patients in a Phase II study of ONYX-015 with chemotherapy showed a tumor reduction of more than 50 percent — and two patients experienced complete reversals.

The tenth person demonstrated a regression of 40 percent. The results were presented Monday at the American Society of Clinical Oncology (ASCO) in Los Angeles.

So far, no patient has shown any disease progression and all are still receiving treatment. By comparison, the recurrence rate of patients who only receive chemotherapy is about 35 percent.

Onyx, of Richmond, Calif., also reported on another Phase II trial (with 14 patients) and updated a Phase Ib trial (with nine patients) where ONYX-015 alone was given. The results showed 30 percent of the 23 patients displayed significant tumor regression, with two having complete regressions.

Drug Attacks p53-Deficient Tumor Cells

ONYX-015, is a genetically engineered adenovirus that has been shown to replicate in and kill tumor cells deficient in p53 tumor-suppressor gene activity. A mutation in p53 is the most common type of genetic abnormality in cancer, showing up in more than half of all tumors — including more than 70 percent of recurrent and refractory cancers of the head and neck.

"We have to say that the results deal only with 10 patients (in the trial that combined ONYX-015 with chemotherapy) and it's too soon to tell the response rate," said Hollings Renton, president and CEO. "But clearly we're excited about the preliminary results. They are encouraging and it gives us the significant motivation to try to rapidly get enrollment in the study to 30 patients where it will be statistically significant."

That trial started 19 weeks ago and involved patients with tumors of the head and neck who may or may not have had prior chemotherapy. However, all failed other forms of up-front treatment, such as surgery and radiation.

In the study, patients received a combination of ONYX-015 with cisplatin and 5-FU, the standard chemotherapeutic agents used in treating head and neck cancers. The treatment consisted of directly injecting the Onyx drug into the tumor for five consecutive days and giving 5-FU intravenously for the same five days. On the first day of the treatment cycle, cisplatin was administered. After a two-week wait, the treatment began again.

"There are not a lot of good therapeutic remedies for head and neck cancer," said Renton. "Usually the duration before reoccurrence is quite short — four to five months. And the survival time is pretty short. It's a negative prognosis."

Of those receiving only ONYX-015 — a larger group than those combining it with chemotherapy — antitumoral activity now has been clearly observed and a high level of safety firmly established, Renton noted.

"We're going to be looking at all the data in all the trials and try to find the regimen with the most efficacy," said Renton. The company expects to begin evaluating the drug in Phase III trials by mid-1999.

Onyx also reported data from two Phase I safety trials of ONYX-015 in pancreatic and gastrointestinal cancers that have metastasized to the liver. The studies found that ONYX-015 was safe and well-tolerated. In the gastrointestinatinal cancer trial, findings showed the drug to be biologically active. Based on these results, Onyx will initiate further studies using different routes of administration and regimes, including combining ONYX-015 with standard chemotherapy. *

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