A Phase II clinical trial in patients with metastatic melanoma using intravenous administration of anonattenuated reovirus type-3 Dearing(RT3D; Reolysin(?,Oncolytics Biotech Inc) in combination with carboplatin and paclitaxel (NCT00984464) met primary endpoint for the first stage of the trial. Reolysin is alaboratory strain of a ubiquitous common environmental virus commonly infecting the respiratory and GI tracts of humans without major sequelae. The Principal Investigator for the trial was Devalingam Mahalingam, M.D., Ph.D., MRCP(UK), MRCP(I), clinical investigator in GI/thoracic oncology and drug development at the Cancer Therapy & Research Center at the University of Texas Health Science Center (CTRC).
Eligible patients include those with metastatic malignant melanoma, a tumor of melanocytes which make the pigment melanin,
who have failed one or more prior therapies or those not considered a candidate for standard first line therapy. The primary objective of the Phase II trial is to assess the anti-tumor effect of the treatment regimen in the study population in terms of objective response rates. The secondary objectives of the trial is to assess progression-free survival (PFS) and overall survival (OS) for the treatment regimen; the disease control rate, including complete response (CR) plus partial response (PR) plus stable disease (SD), and duration, and to assess the safety and tolerability of the treatment regimen in the study population.
Two stage design
The study is a two stage design. Up to 18 evaluable patients with metastatic melanoma were to be treated in the first stage. If three or more patients demonstrated a PR or better, the study could then proceed to the second stage, with up to 43 patients being treated in the entire study. This endpoint was met after 14 evaluable patients were enrolled. Three of 14 patients exhibited a PR, and an additional seven patients had SD for a disease control rate of 71.5%.
Stable disease outcomes
Previous clinical rials have shown that human melanoma cell lines are highly permissive to reovirus type 3 Dearing in in vitro experiments. Ongoing research has also shown that intravenous administration of the virus as a monotherapy resulted in significant tumour growth retardation. A subsequent Phase II monotherapy intravenous administration clinical study demonstrated viral replication in biopsy samples of patients. A Phase I all comers intravenous administration clinical study in combination with docetaxel demonstrated partial response and stable disease outcomes in a small (four) melanoma patient subpopulation.
“These preliminary results are very encouraging and support progressing to subsequent studies,” noted Brad Thompson, President and CEO of Oncolytics. “Past clinical research has shown that Reolyson delivered intravenously replicates in melanoma tumors, and this is the second clinical study to demonstrate responses in patients with Reolysin in combination with other therapeutics.”
Changing the way how cancer is treated
“The emergence of genotyping and increasingly targeted therapies is changing how cancer is treated,”Mahalingam noted. “As a result of recent and potential additional near-term changes to the standard of care for the treatment of melanoma which include agents targeting B-Raf and PD-1,” he said. Based on the changing needs, Oncolytics is now conducting research to evaluate Reolysin in combination with other emerging treatments for a number of patient sub-populations. The Company intends to continue with a follow-up clinical study in melanoma once this research is concluded. On that basis, the second stage of this clinical trial will not proceed at this time.
For more information:
Reolysin Mechanism of Action [Read Article]
–NCT00984464 – Study of Reolysin? in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
Photo:Devalingam Mahalingam, M.D., Ph.D. Photo Courtesy:Cancer Therapy & Research Center at the University of Texas Health Science Center.
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