• DOI:10.1200/JCO.2016.67.1529
• Corpus ID: 27016332

Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.

@article{Puzanov2016TalimogeneLI,
  title={Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.},
  author={Igor Puzanov and Mohammed M Milhem and David R. Minor and Omid Hamid and Ai Li and Lisa Chen and Michael A. Chastain and Kevin S. Gorski and Abraham A. Anderson and Jeffrey Chou and Howard L. Kaufman and Robert H. I. Andtbacka},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  year={2016},
  volume={34 22},
  pages={
          2619-26
        }
}

• I. Puzanov, M. Milhem, +9 authors R. Andtbacka
• Published 27 September 2016
• Medicine, Biology
• Journal of clinical oncology : official journal of the American Society of Clinical Oncology

PURPOSE
Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma.

METHODS
In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (10(6) plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (10(8) plaque-forming units/mL). Ipilimumab (3 mg/kg) was administered intravenously every 3 weeks for four infusions, beginning in week 6. The primary end point was incidence of dose-limiting toxicities. Secondary end points were objective response rate by immune-related response criteria and safety.

RESULTS
Median duration of treatment with T-VEC was 13.3 weeks (range, 2.0 to 95.4 weeks). Median follow-up time for survival analysis was 20.0 months (1.0 to 25.4 months). Nineteen patients were included in the safety analysis. No dose-limiting toxicities occurred, and no new safety signals were detected. Grade 3/4 treatment-related adverse events (AEs) were seen in 26.3% of patients; 15.8% had AEs attributed to T-VEC, and 21.1% had AEs attributed to ipilimumab. The objective response rate was 50%, and 44% of patients had a durable response lasting ≥ 6 months. Eighteen-month progression-free survival was 50%; 18-month overall survival was 67%.

CONCLUSION
T-VEC with ipilimumab had a tolerable safety profile, and the combination appeared to have greater efficacy than either T-VEC or ipilimumab monotherapy.