PMID- 27298410 OWN - NLM STAT- MEDLINE DCOM- 20170727 LR - 20220408 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 34 IP - 22 DP - 2016 Aug 1 TI - Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. PG - 2619-26 LID - 10.1200/JCO.2016.67.1529 [doi] AB - 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. CI - (c) 2016 by American Society of Clinical Oncology. FAU - Puzanov, Igor AU - Puzanov I AD - 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. FAU - Milhem, Mohammed M AU - Milhem MM AD - 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. FAU - Minor, David AU - Minor D AD - 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. FAU - Hamid, Omid AU - Hamid O AD - 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. FAU - Li, Ai AU - Li A AD - 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. FAU - Chen, Lisa AU - Chen L AD - 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. FAU - Chastain, Michael AU - Chastain M AD - 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. FAU - Gorski, Kevin S AU - Gorski KS AD - 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. FAU - Anderson, Abraham AU - Anderson A AD - 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. FAU - Chou, Jeffrey AU - Chou J AD - 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. FAU - Kaufman, Howard L AU - Kaufman HL AD - 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. FAU - Andtbacka, Robert H I AU - Andtbacka RH AD - 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. LA - eng SI - ClinicalTrials.gov/NCT01740297 PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20160613 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antibodies, Monoclonal) RN - 0 (Ipilimumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage MH - Female MH - Humans MH - Ipilimumab MH - Male MH - Melanoma/*therapy MH - Middle Aged MH - Oncolytic Virotherapy/adverse effects/methods MH - *Oncolytic Viruses MH - Skin Neoplasms/*therapy MH - T-Lymphocyte Subsets/immunology MH - Tumor Burden PMC - PMC7189507 COIS- 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. EDAT- 2016/06/15 06:00 MHDA- 2017/07/28 06:00 PMCR- 2017/08/01 CRDT- 2016/06/15 06:00 PHST- 2016/06/15 06:00 [entrez] PHST- 2016/06/15 06:00 [pubmed] PHST- 2017/07/28 06:00 [medline] PHST- 2017/08/01 00:00 [pmc-release] AID - JCO.2016.67.1529 [pii] AID - 671529 [pii] AID - 10.1200/JCO.2016.67.1529 [doi] PST - ppublish SO - J Clin Oncol. 2016 Aug 1;34(22):2619-26. doi: 10.1200/JCO.2016.67.1529. Epub 2016 Jun 13.