Investigational Immunotherapy Falters in Late-Stage Melanoma Trial

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The investigational immunotherapy Allovectin (velimogene aliplasmid) failed to meet key endpoints in a phase III trial.

The investigational immunotherapy Allovectin (velimogene aliplasmid) failed to meet key endpoints in a phase III trial in patients with stage III/IV metastatic melanoma and will no longer be developed.

Allovectin did not demonstrate a statistically significant improvement in objective response rate at ≥24 weeks, its primary endpoint, or in overall survival, the secondary endpoint, when compared with first-line chemotherapy, Vical Incorporated, the drug’s manufacturer said. No further details were released.

“We are disappointed that the trial did not meet either the primary or secondary efficacy endpoints, even though we believe it was well-designed and well-executed,” said Vijay B. Samant, president and chief executive officer of Vical, in a statement. “Based on this outcome, we are terminating the Allovectin program and focusing our resources on our infectious disease vaccine programs.”

The agent, also called Allovectin-7, is a plasmid-based immunotherapeutic that expresses theHLA-B7and β2 microglobulin genes, forming a major histocompatibility (MHC) class I complex. Researchers believe it has multiple mechanisms of action, including immune responses that target treated and distal lesions.¹Designed to be injected directly into lesions as an outpatient treatment, Allovectin was being evaluated as an alternative to chemotherapy. In the phase III trial, 390 patients were randomized to receive either Allovectin (2-mg intralesional injection into a single lesion weekly for six consecutive weeks, repeated beginning after each eighth week), or a regimen of either dacarbazine (1000 mg/m²intravenous infusion over 60 minutes, repeated every 28 days), or temozolomide (150-200 mg/m²orally once daily for five consecutive days, repeated every 28 days).

The negative trial results come at a time when immunotherapies are generating considerable excitement in the field of cancer treatment, particularly in melanoma. The emerging class of inhibitors targeting the PD-1/PD-L1 pathways was among the highlights of the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Allovectin, which would have been a first-in-class agent, had demonstrated encouraging results in patients with advanced melanoma prior to this week’s announcement. In a phase II trial, 15 of 127 evaluable patients achieved an objective response (11.8%; 95% CI, 6.2—17.4) with a median duration of response of 13.8 months (95% CI, 8.5– not estimable).²A histological examination of tissue from two patients whose lesions were resected found no evidence of melanoma.

References

1. Doukas J, Rolland A. Mechanisms of action underlying the immunotherapeutic activity of Allovectin in advanced melanoma [published online ahead of print October 5, 2012].Cancer Gene Ther. 2012;19(12):811-817.
2. Bedikian AY, Richards J, Kharkevitch D, et al. A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma.Melanoma Res. 2010;20(3):218-226.