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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
  1. Pablo Fernandez-Penas1,
  2. Matteo Carlino1,
  3. Katy Tsai2,
  4. Victoria Atkinson3,
  5. Monaster Shaheen4,
  6. Sajeve Thomas5,
  7. Catalin Mihalcioiu6,
  8. Tom Van Hagen7,
  9. Rachel Roberts-Thomson8,
  10. Andrew Haydon9,
  11. Andrew Mant10,
  12. Marcus Butler11,
  13. Gregory Daniels12,
  14. Elizabeth Buchbinder13,
  15. John Hyngstrom14,
  16. Mecker Moller15,
  17. Igor Puzanov16,
  18. C Lance Cowey17,
  19. Eric Whitman18,
  20. Carmen Ballesteros-Merino19,
  21. Shawn Jensen19,
  22. Bernard Fox19,
  23. Emmett Schmidt20,
  24. Clemens Krepler20,
  25. Scott Diede20,
  26. Erica Browning21,
  27. Reneta Hermiz21,
  28. Lauren Svenson21,
  29. Jon Salazar21,
  30. Jack Lee21,
  31. Christopher Baker21,
  32. Donna Bannavong21,
  33. Jendy Sell21,
  34. Kellie Malloy Foerter21,
  35. David Canton21,
  36. Sandra Aung21,
  37. Christopher Twitty21,
  38. Alain Algazi2 and
  39. Adil Daud2
  1. 1Westmead Hospital, University of Sydney, Westmead, Australia
  2. 2University of California, San Francisco, San Francisco, CA, USA
  3. 3Princess Alexandra Hospital, University of Queensland, Woolloongabba, Australia
  4. 4University of Arizona, Tucson, AZ, USA
  5. 5UF Health Cancer Center at Orlando Health, Orlando, FL, USA
  6. 6McGill University Health Centre, Montreal, Canada
  7. 7St. John of God Hospital, Subiaco, Australia
  8. 8Adelaide Oncology and Haematology, Adelaide, Australia
  9. 9The Alfred Hospital, Victoria, Australia
  10. 10Box Hill Hospital, Box Hill, Australia
  11. 11Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  12. 12University of California, San Diego, La Jolla, CA, USA
  13. 13Dana Faber Cancer Institute, Boston, MA, USA
  14. 14University of Utah Healthcare Huntsman Cancer Institute, Salt Lake City, UT, USA
  15. 15University of Miami Sylvester Cancer Center, Miami, FL, USA
  16. 16Roswell Park Cancer Institute, Buffalo, NY, USA
  17. 17Baylor University Medical Center, Dallas, TX, USA
  18. 18Atlantic Health System, Morristown, NJ, USA
  19. 19Earle A. Chiles Research Institute, Portland, OR, USA
  20. 20Merck and Co., Inc., Kenilworth, NJ, USA
  21. 21Oncosec Medical Incorporated, San Diego, CA, USA


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-1

Abstract 799 Figure 2

Percent change in sum of target lesions over time

Conclusions 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#03132675

Ethics 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.


  1. Algazi 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.

  2. 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.

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