RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP A477
OP A478
DO 10.1136/jitc-2020-SITC2020.0799
VO 8
IS Suppl 3
A1 Pablo Fernandez-Penas
A1 Matteo Carlino
A1 Katy Tsai
A1 Victoria Atkinson
A1 Monaster Shaheen
A1 Sajeve Thomas
A1 Catalin Mihalcioiu
A1 Tom Van Hagen
A1 Rachel Roberts-Thomson
A1 Andrew Haydon
A1 Andrew Mant
A1 Marcus Butler
A1 Gregory Daniels
A1 Elizabeth Buchbinder
A1 John Hyngstrom
A1 Mecker Moller
A1 Igor Puzanov
A1 C Lance Cowey
A1 Eric Whitman
A1 Carmen Ballesteros-Merino
A1 Shawn Jensen
A1 Bernard Fox
A1 Emmett Schmidt
A1 Clemens Krepler
A1 Scott Diede
A1 Erica Browning
A1 Reneta Hermiz
A1 Lauren Svenson
A1 Jon Salazar
A1 Jack Lee
A1 Christopher Baker
A1 Donna Bannavong
A1 Jendy Sell
A1 Kellie Malloy Foerter
A1 David Canton
A1 Sandra Aung
A1 Christopher Twitty
A1 Alain Algazi
A1 Adil Daud
YR 2020
UL http://jitc.bmj.com/content/8/Suppl_3/A477.2.abstract
AB 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.