Author: Catherine Hollingsworth

Oncolytics Biotech Inc. reached agreement with the FDA on the design of a Phase III trial of Reolysin in head and neck cancer, marking the first such agreement for an intravenously administered oncolytic virus.

The Phase III trial will be conducted in two stages and will cost an estimated $15 million, Matt Coffey, Oncolytics’ chief operating officer, told BioWorld Today. The Calgary, Alberta-based company has the cash to get through the first half of the study on its own, but it hopes to secure a partner to take Reolysin the rest of the way, he said.

The trial uses an adaptive design in which “the endpoint is not fixed going in,” CEO Brad Thompson said during a conference call. He said it was “a major advantage” getting the FDA to sign off on the study design up front under a special protocol assessment.

Thompson said that the adaptive design already is in use in the area of infectious disease, and he said he believes that there will be “a big push” by the FDA for more adaptive trials to be conducted in oncology.

The trial will assess the intravenous administration of Reolysin with the chemotherapy combination of paclitaxel and carboplatin vs. chemotherapy alone. The drug likely will be studied in about 275 patients whose cancer has progressed while on or after prior platinum-based chemotherapy.

The first stage of the trial is nonadaptive and is designed to enroll 80 patients. The second stage is adaptive, and is designed to enroll between 100 and 400 patients with the most probable statistical enrollment being 195 patients.

According to Oncolytics, the Phase III adaptive trial allows frequent data evaluation to determine if the probability of reaching a statistically significant endpoint has been achieved.

The primary endpoint for the trial is overall survival, and secondary endpoints include progression-free survival, objective response rate (complete response plus partial response) and duration of response and safety and tolerability of Reolysin when administered in combination with paclitaxel and carboplatin.

The decision to pursue a Phase III trial in head and neck cancers was based on positive results seen in preclinical work and the company’s UK Phase I and Phase II combination studies of Reolysin and paclitaxel/carboplatin. Interim results of the U.K. Phase I/II trial reported in March demonstrated an overall response rate of 42 percent and a total clinical benefit rate of 75 percent. Updated Phase II results are expected to be presented later this quarter.

First-in-class Reolysin, a proprietary formulation of the reovirus, could be “as significant as the introduction of the antibody therapy,” Coffey said.

Reolysin is designed to replicate in cancer cells that have an activated RAS pathway, seen in about two-thirds of all cancers. Oncolytics sees an opening with Reolysin in metastatic cancers, including colorectal and non-small-cell lung cancers, and in patients with a mutated KRAS gene who are unlikely to respond to treatment with anti-EGFR monoclonal antibodies.

Under recent labeling revisions, the EGFR class of antibodies is not recommended in colorectal patients who have KRAS mutations in their tumors because they do not respond to EGFR-blocking antibodies.

Head and neck cancer is primarily treated with radiation and surgery and chemotherapy is typically used in advanced cases.

Oncolytics has several other ongoing clinical trials of Reolysin, including a Phase II study in NSCLC with K-RAS or EGFR-activated tumors.

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