TY - JOUR T1 - 799 Durable responses and immune activation with intratumoral electroporation of pIL-12 plus pembrolizumab in actively progressing anti-PD-1 refractory advanced melanoma: KEYNOTE 695 interim data JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer SP - A477 LP - A478 DO - 10.1136/jitc-2020-SITC2020.0799 VL - 8 IS - Suppl 3 AU - Pablo Fernandez-Penas AU - Matteo Carlino AU - Katy Tsai AU - Victoria Atkinson AU - Monaster Shaheen AU - Sajeve Thomas AU - Catalin Mihalcioiu AU - Tom Van Hagen AU - Rachel Roberts-Thomson AU - Andrew Haydon AU - Andrew Mant AU - Marcus Butler AU - Gregory Daniels AU - Elizabeth Buchbinder AU - John Hyngstrom AU - Mecker Moller AU - Igor Puzanov AU - C Lance Cowey AU - Eric Whitman AU - Carmen Ballesteros-Merino AU - Shawn Jensen AU - Bernard Fox AU - Emmett Schmidt AU - Clemens Krepler AU - Scott Diede AU - Erica Browning AU - Reneta Hermiz AU - Lauren Svenson AU - Jon Salazar AU - Jack Lee AU - Christopher Baker AU - Donna Bannavong AU - Jendy Sell AU - Kellie Malloy Foerter AU - David Canton AU - Sandra Aung AU - Christopher Twitty AU - Alain Algazi AU - Adil Daud Y1 - 2020/11/01 UR - http://jitc.bmj.com/content/8/Suppl_3/A477.2.abstract N2 - Background Electroporated plasmid IL-12 (TAVO or tavokinogene telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize with anti-PD-1 antibodies in patients predicted as non-responders to anti-PD-1.1 2 Interim data from patients with stage III/IV melanoma actively progressing on anti-PD-1 antibody are presented herein.Methods Patients with confirmed disease progression by RECIST v1.1 after at least 12 weeks of treatment on pembrolizumab or nivolumab (or combination checkpoint blockade) and within 12 weeks of last dose (with no intervening therapies) were enrolled. There was no limit on the number of prior lines of therapy. At least one accessible lesion was electroporated with plasmid IL-12 (pIL-12-EP) on days 1, 5 and 8 every 6 weeks and pembrolizumab was administered every 3 weeks. Tumor response in treated and untreated lesions was assessed by RECIST v1.1 every 12 weeks. Endpoints include ORR, safety, PFS, OS, and DOR.Results The first 56 patients treated of 100 planned were included in this interim analysis. Of these, 84% had Stage IV disease, 30% had M1c or M1d disease, and 27% had prior exposure to ipilimumab. In 54 efficacy evaluable patients the investigator-assessed ORR was 30% (3 CR/13 PR), 5 patients had 100% reduction of target lesions. All responses have been confirmed, only two responding patient progressed while on study, 2 patients completed the study with ongoing responses (figures 1 and 2). In patients with M1c/M1d disease, the ORR was 35.2% (n=6/17). Tumor reduction was observed in untreated lesions in 12 of 12 patients who had unaccessible lesions or accessible untreated lesions. The median overall survival (mOS) and duration of response (mDOR) has not been reached, with a median follow-up time of 13 months. Grade 3 treatment-related adverse events (TRAEs) were seen in 5.4% of patients, and there were no grade 4/5 TRAEs. The rate of grade 3 treatment-emergent (TEAEs) regardless of cause was 23.2%. The median time for pIL-12-EP treatment was 10 minutes (range 2,46). Consistent with prior studies of single-agent pIL-12-EP, tumor IHC, and transcriptomic assessments revealed hallmarks of antigen-specific antitumor immunity in this study. Additional analyses including microbiome, TCR clonality, and peripheral blood biomarker assays will be presented.Abstract 799 Figure 1 Best confirmed overall response by RECIST v1.1 after confirmed progression on anti PD-1Abstract 799 Figure 2 Percent change in sum of target lesions over timeConclusions In this rigorously defined PD-1 antibody refractory patient population, the addition of pIL-12-EP to PD-1 antibody therapy induced deep, durable, systemic response in local treated and distant visceral metastatic untreated lesions with nominal systemic toxicity.Trial Registration Trial Registration: NCT#03132675Ethics Approval The study was approved by a central IRB and/or local institutional IRBs/Ethics Committees as required for each participating institution.Consent Written informed consent was obtained from the patients participating within the trial, the current abstract does not contain sensitive or identifiable information requiring an additional consent from patients.ReferencesAlgazi A, Bhatia S, Agarwala S, et al. Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients. Annals of Oncology 2019;31:532–540.Algazi A, Twitty C, Tsai K, et al. Phase II trial for IL-12 plasmid transfection and PD-1 blockade in immunologically quiescent melanoma. Clinical Cancer Research 2020;26:2827-2837. ER -