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Oncothyreon (ONTY) Reports Data for Two PX-866 Phase 1/2s

November 14, 2011 6:56 AM EST
Oncothyreon Inc. (Nasdaq: ONTY) presented data from two Phase 1/2 trials of PX-866, an irreversible, pan-isoform phosphatidylinositol-3-kinase (PI-3K) inhibitor, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in San Francisco, California. Results presented highlighted findings from the Phase 1 dose-escalation portions of Phase 1/2 trials evaluating PX-866 in combination with docetaxel (Taxotere) and PX-866 in combination with cetuximab (Erbitux).

The Phase 1 portion of the Phase 1/2 trial of PX-866 in combination with the chemotherapeutic agent docetaxel enrolled 43 patients with advanced cancer for whom docetaxel was considered standard of care. Patients were treated at three different dose levels of PX-866 administered daily in combination with the standard dose of docetaxel (75 mg/m2) administered once every three weeks. No dose-limiting toxicities were identified, and the recommended Phase 2 daily dose of PX-866 to be given in combination with docetaxel was determined to be the same as the single agent daily maximum tolerated dose of 8 mg. The combination of PX-866 and docetaxel was generally well-tolerated, with the most adverse events being Grade 1/2 in severity. The safety profile for combination treatment was consistent with that for either drug administered alone. Combination treatment had no impact on the pharmacokinetic profile of either drug.

In 28 patients evaluable for response, best response was stable disease in 21 patients, and progressive disease in seven patients, for a disease control rate of 75 percent. Eight patients have received seven or more cycles of treatment, and 20 patients were reported to be still active on study. The most common reason for discontinuing therapy has been progressive disease. A trend to increased time on study was seen in patients with a mutation in their PIK3CA gene compared to patients without such a mutation.

The Phase 1 portion of the Phase 1/2 trial of PX-866 in combination with cetuximab enrolled 11 patients with either incurable metastatic colorectal carcinoma or incurable progressive, recurrent or metastatic squamous cell carcinoma of the head and neck treated at two different daily dose levels of PX-866 plus the standard weekly dose of cetuximab. No dose-limiting toxicities were identified and the recommended daily dose of PX-866 in combination with cetuximab was determined to be the same as the single agent daily maximum tolerated dose of 8 mg. The combination of PX-866 and cetuximab was generally well-tolerated, with the majority of adverse events Grade 1/2 in severity. PX-866 had no impact on the pharmacokinetic profile of cetuximab as compared to historical data.

Eight patients were evaluable for response per protocol, and four patients had a confirmed partial response, three patients had stable disease and one patient had progressive disease, for a disease control rate of 88 percent. Five of the eight evaluable patients had received prior treatment with an EGFR inhibitor. Among these patients, the best response was one partial response, three stable disease and one progressive disease. The median number of cycles (21 days each) received by all patients was six (range 1-13).

This trial has now advanced to the Phase 2 portion, which is an open-label, randomized evaluation of the antitumor activity and safety of PX-866 administered at the recommended daily dose in combination with cetuximab, versus cetuximab alone, in two groups of patients not previously treated with cetuximab. Group 1 is enrolling patients with metastatic colorectal carcinoma (CRC) who have a history of progression or recurrence following prior treatment with irinotecan and oxaliplatin containing regimens or who are intolerant of irinotecan. Patients with CRC and Kras mutations are excluded from the trial. Group 2 is enrolling patients with incurable squamous cell carcinoma of the head and neck who have a history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen. The two groups will be randomized and evaluated independently. The primary endpoint of the Phase 2 portion is objective response rate based on RECIST criteria. Secondary endpoints include progression free and overall survival, duration of response and disease control rate.


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