Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

1. Robert H.I. Andtbacka, 
2. Howard L. Kaufman⇑, 
3. Frances Collichio,
4. Thomas Amatruda, 
5. Neil Senzer, 
6. Jason Chesney, 
7. Keith A. Delman,
8. Lynn E. Spitler, 
9. Igor Puzanov, 
10. Sanjiv S. Agarwala, 
11. Mohammed Milhem,
12. Lee Cranmer, 
13. Brendan Curti, 
14. Karl Lewis, 
15. Merrick Ross, 
16. Troy Guthrie,
17. Gerald P. Linette, 
18. Gregory A. Daniels, 
19. Kevin Harrington, 
20. Mark R. Middleton,
21. Wilson H. Miller Jr, 
22. Jonathan S. Zager, 
23. Yining Ye, 
24. Bin Yao, 
25. Ai Li,
26. Susan Doleman, 
27. Ari VanderWalde, 
28. Jennifer Gansert and 
29. Robert Coffin

+Author Affiliations

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, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Lynn E. Spitler, Northern California Melanoma Center, San Francisco; Gregory A. Daniels, University of California San Diego Medical Center, Moores Cancer Center, La Jolla; Yining Ye, Bin Yao, Ai Li, Ari Vander Walde, and Jennifer Gansert, Amgen, Thousand Oaks, CA; Igor Puzanov, Vanderbilt University, Nashville, TN; Sanjiv S. Agarwala, St Luke's University Hospital and Health Network, Bethlehem, and Temple University School of Medicine, Philadelphia, PA; Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA; Lee Cranmer, University of Arizona, Tucson, AZ; Brendan Curti, Earle A. Chiles Research Institute, Portland, OR; Karl Lewis, University of Colorado Cancer Center, Aurora, CO; Troy Guthrie, Baptist Cancer Institute, Jacksonville; Jonathan S. Zager, Moffitt Cancer Center, Tampa, FL; Gerald P. Linette, Washington University School of Medicine, St Louis, MO; Kevin Harrington, Institute of Cancer Research, Royal Marsden Hospital, London; Mark R. Middleton, National Institute for Health Research Biomedical Research Centre, Oxford, United Kingdom; Wilson H. Miller Jr, McGill University, Montreal, Quebec, Canada; and Susan Doleman and Robert Coffin, Amgen, Woburn, MA.

1. Corresponding author: Howard L. Kaufman, MD, FACS, Rutgers Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ 08901; e-mail:howard.kaufman@rutgers.edu.

1. Presented in part at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013, and 50th ASCO Annual Meeting, Chicago, IL, May 30-June 3, 2014.

1. R.H.I.A. and H.L.K. contributed equally to this work.

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.

Footnotes

• Written on behalf of the OPTiM investigators.
• Supported by Amgen, which also funded medical writing assistance.
• Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.
• Clinical trial information: NCT00769704.