000K  utf8
1100  $c2023
1500  eng
2050  urn:nbn:de:gbv:8:3-2023-00312-8
2051  10.1136/jitc-2022-006270
3000  Chesney, Jason A
3010  Collichio, Frances A
3010  Friedlander, Philip
3010  Garbe, Claus
3010  Glaspy, John
3010  Hamid, Omid
3010  Hauschild, Axel
3010  Joshi, Harshada
3010  Lebbé, Celeste
3010  Logan, Theodore
3010  Mehnert, Janice M
3010  Milhem, Mohammed M
3010  Puzanov, Igor
3010  Ross, Merrick
3010  Singh, Parminder
3010  Snyder, Wendy
4000  Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial  [Chesney, Jason A]
4209  Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus ipilimumab alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide the longest efficacy and safety follow-up for patients with melanoma treated with a combination of an oncolytic virus and a checkpoint inhibitor.Eligible patients with unresectable stage IIIB‒IV melanoma were randomized 1:1 to receive T-VEC plus ipilimumab or ipilimumab alone. T-VEC was administered intralesionally at 106 plaque-forming units (PFU)/mL in week 1, followed by 108 PFU/mL in week 4 and every 2 weeks thereafter. Ipilimumab (3 mg/kg every 3 weeks; ≤4 doses) was administered intravenously starting at week 1 in the ipilimumab arm and week 6 in the combination arm. The primary end point was investigator-assessed objective response rate (ORR) per immune-related response criteria; key secondary end points included durable response rate (DRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Overall, 198 patients were randomized to receive the combination (n=98) or ipilimumab (n=100). The combination improved the ORR versus ipilimumab (35.7% vs 16.0%; OR 2.9; 95% CI 1.5 to 5.7; p=0.003). DRR was 33.7% and 13.0% (unadjusted OR 3.4; 95% CI 1.7 to 7.0; descriptive p=0.001), respectively. Among the objective responders, the median DOR was 69.2 months (95% CI 38.5 to not estimable) with the combination and was not reached with ipilimumab. Median PFS was 13.5 months with the combination and 6.4 months with ipilimumab (HR 0.78; 95% CI 0.55 to 1.09; descriptive p=0.14). This is the first randomized controlled study of the combination of an oncolytic virus and a checkpoint inhibitor that meets its primary end point.Trial registration number: NCT01740297.
4950  https://doi.org/10.1136/jitc-2022-006270$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2023-00312-8$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00003631
5051  610
5550  Herpesvirus 1, Human
5550  Humans
5550  Immunotherapy
5550  Ipilimumab
5550  Melanoma
5550  Melanoma
5550  Oncolytic Virotherapy
5550  Oncolytic Virotherapy
5550  Oncolytic viruses
5550  Oncolytic Viruses