Neoadjuvant intratumoral plasmid interleukin-12 electro-gene-transfer and nivolumab in patients with operable locoregionally advanced melanoma.

Autor:	Tarhini AA; Moffitt Cancer Center, Tampa, Florida, United States., Eroglu Z; Moffitt Cancer Center, Tampa, Florida, United States., Eljilany I; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States., Zager JS; Moffitt Cancer Center, Tampa, Florida, United States., Gonzalez RJ; Moffitt Cancer Center, Tampa, FL, United States., Sarnaik AA; Moffitt Cancer Center, Tampa, FL, United States., Cruse CW; Moffitt Cancer Center, Tampa, Florida, United States., Khushalani NI; Moffitt Cancer Center, Tampa, FL, United States., De Aquino DB; Moffitt Cancer Center, Tampa, Florida, United States., Abraham E; Moffitt Cancer Center, Tampa, Florida, United States., Acevedo DM; Moffitt Cancer Center, Tampa, Florida, United States., Richards A; Moffitt Cancer Center, Tampa, FL, United States., Schell MJ; Moffitt Cancer Center, Tampa, FL, United States., Kalos D; Moffitt Cancer Center, Tampa, United States., Chen PL; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States., Messina JL; Moffitt, Tampa, FL, United States., Canton DA; OncoSec Medical Incorporated, San Diego, CA, United States., Sondak VK; Moffitt Cancer Center, Tampa, FL, United States.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Oct 17. Date of Electronic Publication: 2024 Oct 17.
DOI:	10.1158/1078-0432.CCR-24-2768
Abstrakt:	Purpose: Intratumoral (IT) TAVO-EP (tavokinogene telseplasmid delivered by electroporation) results in localized expression of interleukin-12 (IL-12) within the tumor microenvironment (TME). This study evaluated neoadjuvant TAVO-EP combined with intravenous (IV) nivolumab followed by surgery and adjuvant nivolumab in patients with operable locoregionally advanced melanoma. Patients and Methods: The neoadjuvant phase comprised up to 3 Χ 4-week cycles where TAVO-EP was given IT on days 1, 8, and 15 (optional) concurrently with 480 mg nivolumab IV on day 8 of each 4-week cycle. Surgery followed, and adjuvant nivolumab was initiated after surgery. The primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathological response (MPR; pCR or near pCR). Results: Sixteen patients were enrolled and the preoperative radiological response rate was 63%. One patient declined surgery after experiencing a significant clinical response. Among the remaining 15 patients, pCR rate was 60% and MPR was 80%. No patient with MPR has had disease recurrence with a median follow-up from the date of surgery of 15.4 months. At baseline, most patients exhibited low CD8+ TIL, PD-L1 and IFN-γ gene expression signature. There was enhanced immune activation following treatment in the TME and blood including increased immune-related gene expression, CD8+ TIL and proliferating immune cell subsets. Conclusions: The clinical efficacy of neoadjuvant IT TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti-PD1 based regimens.
Databáze:	MEDLINE
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