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J Clin Oncol. 2016 Aug 1;34(22):2619-26. doi: 10.1200/JCO.2016.67.1529. Epub 2016 Jun 13.

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

Author information

1
Igor Puzanov, Vanderbilt University, Nashville, TN; Mohammed M. Milhem, University of Iowa, Iowa City, IA; David Minor, California Pacific Melanoma Center, San Francisco; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles; and Ai Li, Lisa Chen, Michael Chastain, Kevin S. Gorski, Abraham Anderson, and Jeffrey Chou, Amgen, Thousand Oaks, CA; Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; and Robert H.I. Andtbacka, University of Utah, Salt Lake City, UT. igor.puzanov@vanderbilt.edu.
2
Igor Puzanov, Vanderbilt University, Nashville, TN; Mohammed M. Milhem, University of Iowa, Iowa City, IA; David Minor, California Pacific Melanoma Center, San Francisco; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles; and Ai Li, Lisa Chen, Michael Chastain, Kevin S. Gorski, Abraham Anderson, and Jeffrey Chou, Amgen, Thousand Oaks, CA; Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; and Robert H.I. Andtbacka, University of Utah, Salt Lake City, UT.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01740297.

PMID:
27298410
DOI:
10.1200/JCO.2016.67.1529
[Indexed for MEDLINE]

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