Oncolytic immunotherapy improved durable response, survival in metastatic melanoma

CHICAGO — Talimogene laherparepvec demonstrated a statistically significant improvement in durable response rate compared with granulocyte-macrophage colony-stimulating factor among patients with unresected stage IIIB/C and IV melanoma, according to results of a phase 3 study presented at the ASCO Annual Meeting.

An interim analysis also showed a trend toward improved OS with talimogene laherparepvec (HR=0.79; 95% CI, 0.61-1.02).

Robert H.I. Andtbacka

“Over the last 30 years, the incidence of metastatic melanoma has increased by over 200 percent, so there is a need for new treatment options,” Robert H.I. Andtbacka, MD, assistant professor at the University of Utah Huntsman Cancer Institute, said in a press release. “The results of this study are encouraging in a disease as devastating as metastatic melanoma.”

Talimogene laherparepvec [T-VEC (Amgen)] is an oncolytic immunotherapy derived from herpes simplex virus type-1.

Upon injection directly into tumor tissue, T-VEC selectively infects and replicates in tumor cells. The virus replication leads to tumor cell lysis and exposure of tumor-specific antigens to the immune system, resulting in a local and systemic immune activation and an immune-mediated destruction of tumor cells throughout the body.

T-VEC also is engineered to produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance the local and systemic antitumor immune response.

The OPTiM trial included 436 patients (median age, 63 years; 57% men) with unresected melanoma with regional or distant metastasis.

Researchers randomly assigned patients to receive T-VEC intralesionally every 2 weeks (n=295) or GM-CSF subcutaneously for the first 14 days of each 28-day cycle (n=141).

Treatment lasted up to 18 months. Patients with stable disease and those who responded to therapy were eligible for additional treatment on an extension protocol.

Durable response rate, defined as partial or complete response lasting continuously for at least 6 months, served as the primary endpoint.

Researchers reported higher objective response rates (26% vs. 6%) and complete response rates (11% vs. 1%) among patients assigned to T-VEC.

T-VEC also was associated with a statistically significant improvement in durable response rate (16% vs. 2%). Patients with earlier-stage disease had the highest rates of durable response.

T-VEC demonstrated a tolerable safety profile, according to researchers.

Serious adverse events occurred in 26% of patients assigned to T-VEC and 13% of patients assigned to GM-CSF. The most common adverse events reported in the T-VEC arm were fatigue, chills and pyrexia.

For more information:

Andtbacka RHI. Abstract #LBA9008. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.

Disclosure: The researchers report research funding/honoraria from, consultant/advisory roles with, employment or leadership positions with, or stock ownership in Amgen, BioVex, Bristol-Myers Squibb, GlaxoSmithKline, Morphotek and Roche/Genentech.