Efficacy and safety results of phase 2 studies provide support for undertaking pivotal trials investigating an oncolytic vaccine therapy, granulocyte colony-stimulating factor (GM-CSF)-encoding oncolytic herpes simplex virus (OncoVEX GM-CSF, BioVex), for treating metastatic melanoma (MM) and head and neck squamous cell carcinoma (SCC).
National report - Efficacy and safety results of phase 2 studies provide support for undertaking pivotal trials investigating an oncolytic vaccine therapy, granulocyte colony-stimulating factor (GM-CSF)-encoding oncolytic herpes simplex virus (OncoVEXGM-CSF, BioVex), for treating metastatic melanoma (MM) and head and neck squamous cell carcinoma (SCC).
The phase 3 study (OPTiM) investigating OncoVEXGM-CSF for the treatment of MM was launched in May 2009. As of June 2010, more than half of the planned recruitment of 360 patients had been enrolled. Total enrollment is slated for completion at the end of 2010, and first results of the study should be available during 2011. The sponsor hopes that the phase 3 study of treatment of head and neck SCC will be under way in the last quarter of 2010.
Melanoma study details
The phase 2 MM study enrolled 50 patients with stage IIIC and IV disease, three-fourths of whom had received prior nonsurgical therapy. They were treated open-label with the intratumoral vaccine at baseline, three weeks later and then once every two weeks for a maximum of 24 injections. Results showed 10 patients (20 percent) achieved a complete response; another four (8 percent) patients were partial responders; and two (4 percent) additional patients had a complete response after surgery.
Responses have persisted in more than 90 percent of patients, with follow-up extending between seven months and up to four-and-a-half years in the earliest treated patient who had liver and lung metastases at study enrollment.
"The complete response rate achieved in the phase 2 study is arguably better than any obtained before for patients with such advanced disease, and the longevity of the responses in this population with an overall poor prognosis is notable as well," says Howard Kaufman, M.D., Rush Cancer Program director, Rush University, Chicago, and principal investigator for the phase 3 study.
The phase 3 study is an international multicenter study. Centers are currently active in the United States and United Kingdom, and are expected to be added in Canada and South Africa. The study is randomizing patients 2-to-1 to intratumoral OncoVEXGM-CSF or subcutaneous GM-CSF. In contrast to the phase 2 study, enrollment also includes patients with unresectable stage IIIb disease (as well as IIIc as for phase 2), and for stage IV melanoma, those with the most advanced M1c disease are not included.
Head and neck SCC
The planned phase 3 study of head and neck SCC will involve 400 patients enrolled at sites across the United States and United Kingdom. Eligible patients will have advanced nodal disease and be randomized to standard therapy with radiation plus cisplatin or the combination with OncoVEXGM-CSF .
Previous clinical trial experience with OncoVEXGM-CSF in this indication consists of a study enrolling 17 patients. Among the subgroup that received the dose that is being taken forward into the pivotal trial, all patients achieved a complete pathologic response, defined as no viable tumor found when patients went for surgery after oncolytic vaccine therapy. Furthermore, with all patients followed for at least two years and up to four years, there have been no locoregional relapses. DT
Disclosures: Dr. Coffin is an employee and stockholder of BioVex. Dr. Kaufman reports no relevant financial interests.