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383 Durable responses with intratumoral electroporation of plasmid interleukin 12 plus pembrolizumab in patients with advanced melanoma progressing on an anti-PD-1 antibody: updated data from keynote 695
  1. Pablo Fernandez-Penas1,
  2. Matteo Carlino2,
  3. Katy Tsai3,
  4. Victoria Atkinson4,
  5. Monaster Shaheen5,
  6. Sajeve Thomas6,
  7. Catalin Mihalcioiu7,
  8. Tom Van Hagen8,
  9. Rachel Roberts-Thomson9,
  10. Andrew Haydon10,
  11. Andrew Mant11,
  12. Marcus Butler12,
  13. Gregory Daniels3,
  14. Elizabeth Bunchbinder13,
  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. Scott Diede20,
  25. Rebecca Setta21,
  26. Jendy Sell21,
  27. David Canton21,
  28. Sandra Aung21,
  29. Christopher Twitty21,
  30. Sunny Xie21,
  31. Ying Lu21,
  32. Bridget O’Keefe21,
  33. Alain Algazi3 and
  34. Adil Daud3
  1. 1Westmead Hospital, University of Sydney, Westmead, Australia
  2. 2Melanoma Institute Australia, Sydney, Australia
  3. 3University of California, San Francisco, CA, USA
  4. 4Princess Alexandra Hospital, University of Queensland, Woolloongabba, Australia
  5. 5University of Arizona, Tucson, AZ, USA
  6. 6UF Health Cancer Center at Orlando Health, Orlando, FL, USA
  7. 7McGill University Health Centre, Montreal, Canada
  8. 8St. John of God Hospital, Subiaco, Australia
  9. 9Adelaide Oncology and Haematology, Adelaide, Australia
  10. 10The Alfred Hospital, Melbourne, Australia
  11. 11Box Hill Hospital, Box Hill, Australia
  12. 12Princess Margaret Cancer Centre, Toronto, Canada
  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 Comprehensive Cancer Center, 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 interleukin-12 (pIL-12-EP; tavokinogene telseplasmid; TAVO) induces sustained intratumoral expression of IL-12, a cytokine that is integral for response to anti-PD-1 antibodies. Here, we present updated safety and response duration data from KEYNOTE 695, a Phase 2, multicenter, open-label trial of pIL-12-EP in combination with pembrolizumab in patients with stage III/IV melanoma immediately following confirmed progression on an anti-PD-1 antibody.

Methods Patients with confirmed disease progression after ≥12 weeks‘ treatment with an anti-PD-1 antibody alone or in combination were eligible. Patients received intratumoral pIL-12-EP on days 1, 5 and 8 every 6 weeks and pembrolizumab 200 mg every 3 weeks. Responses were assessed by the investigator at 12-week intervals using RECIST v1.1; overall survival (OS) and duration of response (DoR) assessments were conducted using the Kaplan-Meier method.

Results Of the first 56 patients treated, 50% had visceral disease (M1b-d), 80% had received 1–2 and 20% ≥3 prior lines of therapy, 27% had prior ipilimumab and 21% prior BRAF/MEK inhibitors. 61% of patients were primary refractory to anti-PD-1. 54 patients were efficacy evaluable, defined as patients who had at least one post-treatment scan. The investigator-assessed objective response rate (ORR) per RECIST was 27.8% (4 CR, 11 PR); ORR per iRECIST was 29.6%. In patients with M1b-d staging, ORR was 33.3% (n=9/27), and in those receiving prior ipilimumab, ORR was 33.3% (n=5/15). Seven patients had 100% reduction in target lesions, and regression was observed in non-injected lesions. The median DoR had not been reached. With a median follow up of 19.3 months, the median OS (95% CI) was 24.5 (14.4, NR) months (figure 1). The study is now fully enrolled. In 105 patients with safety data, there were no Grade 4/5 treatment-related adverse events (TRAEs) reported. Grade 3 TRAEs occurred in 5.7% and comprised cellulitis in two patients and arthralgia, pneumonitis, enteritis, keratoacanthoma, lichen planus and musculoskeletal chest pain in one patient each. The Grade 1/2 TRAEs in ≥10% patients were fatigue (27.6%), procedural pain (20.0%), diarrhea (17.1%), nausea (10.5%) and pruritus (10.5%). ORR by blinded independent central review has commenced and a global phase 3 trial is planned.

Abstract 383 Figure 1

Overall survival in patients treated with pIL-12-EP in combination with pembrolizumab. Dark grey bars: time on study treatment, light grey bars: end of treatment to death or censoring

Conclusions Patients with anti-PD-1 therapy refractory advanced melanoma can achieve deep, durable responses in both injected and non-injected lesions with pIL-12-EP plus pembrolizumab. Intratumoral pIL-12-EP in combination with pembrolizumab was generally well tolerated, with minimal Grade 3 and no Grade 4/5 TRAEs.

Trial Registration NCT03132675

Ethics Approval The study was approved by a central IRB and/or local institutional IRB/Ethics Committee as required for each participating institution.

Consent Written informed consent was obtained from the patients participating in the trial; the current abstract does not include information requiring additional consent

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