Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Author:

Andtbacka Robert H.I.1,Kaufman Howard L.1,Collichio Frances1,Amatruda Thomas1,Senzer Neil1,Chesney Jason1,Delman Keith A.1,Spitler Lynn E.1,Puzanov Igor1,Agarwala Sanjiv S.1,Milhem Mohammed1,Cranmer Lee1,Curti Brendan1,Lewis Karl1,Ross Merrick1,Guthrie Troy1,Linette Gerald P.1,Daniels Gregory A.1,Harrington Kevin1,Middleton Mark R.1,Miller Wilson H.1,Zager Jonathan S.1,Ye Yining1,Yao Bin1,Li Ai1,Doleman Susan1,VanderWalde Ari1,Gansert Jennifer1,Coffin Robert S.1

Affiliation:

1. Robert H.I. Andtbacka, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Frances Collichio, University of North Carolina Medical Center, Chapel Hill, NC; Thomas Amatruda, Minnesota Oncology, Fridley, MN; Neil Senzer, Mary Crowley Cancer Research Center, Dallas; Merrick Ross, University of Texas MD Anderson Cancer Center, Houston, TX; Jason Chesney, University of Louisville, Louisville, KY; Keith A. Delman,...

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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