CHICAGO—Talimogene laherparepvec (T-VEC) represents a novel potential therapeutic option for patients with melanoma and regional or distant metastases, the randomized phase 3 OPTiM trial comparing T-VEC with granulocyte-macrophage colony-stimulating factor (GM-CSF), concluded at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase 3 trial,” said Robert Hans Ingemar Andtbacka, MD, CM, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.

The agent demonstrated both a statistically significant improvement in durable response rate, the primary endpoint, compared with GM-CSF in patients with unresectable stage IIIB-IV melanoma (16.3% vs. 2.1%; hazard ratio [HR], 8.9; P<0.0001) and had a tolerable safety profile; the only grade 3 or 4 adverse event that occurred in more than 2% of patients was cellulitis (2.1%), he said.

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In addition, a planned interim analysis showed a trend toward improved overall survival (OS). Median OS was 23.3 months in the T-VEC arm and 19.0 months in the GM-CSF arm (HR, 0.79; P<0.07). These data represent more than 85% of the required events for the primary analysis of OS; 36-month survival was 40.6% in the T-VEC arm compared with 27.8% in the GM-CSF arm.

The oncolytic immunotherapy is derived from herpes simplex virus type-1 designed to selectively replicate within tumors and to produce GM-CSF to enhance systemic antitumor immune responses, Dr. Andtbacka said.

A total of 684 patients were screened and 436, comprising the intent-to-treat population, were enrolled between May 2009 and July 2011 from 64 sites in the United States, United Kingdom, Canada, and South Africa. Patients were randomly assigned in a 2:1 ratio to T-VEC (n=295) or GM-CSF (n=141). Median age was 63 years; 57% were men, and stage distribution was 30% IIIB/C; 27% IV M1a; 21% IV M1b; and 22%, IV M1c.

Durable response rate by stage (T-VEC, GM-CSF) was IIIB/C (33%, 0%), M1a (16%, 2%), M1b (3%, 4%), and M1c (8%, 3%). The objective overall response was 26.4% in the T-VEC arm (10.8% complete response [CR] and 15.6% partial response [PR]) compared with 5.7% in the GM-CSF arm (0.7% CR; 5.0% PR).

Time to treatment failure, a secondary endpoint, was a median of 8.2 months in the T-VEC arm and 2.9 months in the GM-CSF arm (HR, 0.42; P<0.0001).