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Clinical Trial
. 2015 Sep 1;33(25):2780-8.
doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Robert H I Andtbacka  1 , Howard L Kaufman  2 , Frances Collichio  1 , Thomas Amatruda  1 , Neil Senzer  1 , Jason Chesney  1 , Keith A Delman  1 , Lynn E Spitler  1 , Igor Puzanov  1 , Sanjiv S Agarwala  1 , Mohammed Milhem  1 , Lee Cranmer  1 , Brendan Curti  1 , Karl Lewis  1 , Merrick Ross  1 , Troy Guthrie  1 , Gerald P Linette  1 , Gregory A Daniels  1 , Kevin Harrington  1 , Mark R Middleton  1 , Wilson H Miller Jr  1 , Jonathan S Zager  1 , Yining Ye  1 , Bin Yao  1 , Ai Li  1 , Susan Doleman  1 , Ari VanderWalde  1 , Jennifer Gansert  1 , Robert S Coffin  1
Affiliations
Clinical Trial

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Robert H I Andtbacka et al. J Clin Oncol. .

Abstract

Purpose: Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial.

Patients and methods: Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate.

Results: Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred.

Conclusion: T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

Trial registration: ClinicalTrials.gov NCT00769704.

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