Julia M Greene1, Erika J Schneble1, Doreen O Jackson1, Diane F Hale2, Timothy J Vreeland1, Madeline Flores1, Jonathan Martin1, Garth S Herbert1, Mark O Hardin3, Xianzhong Yu4, Thomas E Wagner5, George E Peoples6,7. 1. General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA. 2. General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA. diane.f.hale.mil@mail.mil. 3. General Surgery Department, Madigan Army Medical Center, 9040 Jackson Ave., Tacoma, 98431, WA, USA. 4. Clemson University, Clemson, SC, USA. 5. Perseus PCI, Greenville, SC, USA. 6. Cancer Vaccine Development Program, 600 Navarro Street, Suite 500, San Antonio, TX, 78205, USA. georgepeoples2@hotmail.com. 7. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. georgepeoples2@hotmail.com.
Abstract
BACKGROUND: Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV melanoma patients. METHODS: Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed. RESULTS: Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2 toxicities were <grade 3. Median overall survival (OS) was 16.1 months with projected 5-year survival = 29 %. Significant OS improvement for patients receiving ≥3 versus <3 inoculations (43.1 vs. 16.7 %, p = 0.02) was observed. Patients with no evidence of disease (NED) showed improved OS (80 vs. 14 %, p = 0.005). No clinicopathologic differences were present between phase I (n = 10) and IIa (n = 15) patients; phase IIa patients received more frequent dosing and higher mean number of inoculations. Phase IIa median OS was significantly higher (23.8 vs. 8.7 months, p = 0.004). CONCLUSIONS: The dendritoma vaccine has minimal toxicity profile with potential clinical benefit. There was OS advantage for NED stage IV patients, those receiving higher number of doses and increased frequency. Based on these results, we initiated a phase IIb trial utilizing improved dendritoma technology in the adjuvant setting for NED stage III/IV melanoma patients.
BACKGROUND: Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV melanomapatients. METHODS: Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed. RESULTS: Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2toxicities were <grade 3. Median overall survival (OS) was 16.1 months with projected 5-year survival = 29 %. Significant OS improvement for patients receiving ≥3 versus <3 inoculations (43.1 vs. 16.7 %, p = 0.02) was observed. Patients with no evidence of disease (NED) showed improved OS (80 vs. 14 %, p = 0.005). No clinicopathologic differences were present between phase I (n = 10) and IIa (n = 15) patients; phase IIa patients received more frequent dosing and higher mean number of inoculations. Phase IIa median OS was significantly higher (23.8 vs. 8.7 months, p = 0.004). CONCLUSIONS: The dendritoma vaccine has minimal toxicity profile with potential clinical benefit. There was OS advantage for NED stage IV patients, those receiving higher number of doses and increased frequency. Based on these results, we initiated a phase IIb trial utilizing improved dendritoma technology in the adjuvant setting for NED stage III/IV melanomapatients.
Authors: Belén P Solans; Ascensión López-Díaz de Cerio; Arlette Elizalde; Luis Javier Pina; Susana Inogés; Jaime Espinós; Esteban Salgado; Luis Daniel Mejías; Iñaki F Trocóniz; Marta Santisteban Journal: Br J Clin Pharmacol Date: 2019-06-14 Impact factor: 4.335
Authors: Shikhar Mehrotra; Carolyn D Britten; Steve Chin; Elizabeth Garrett-Mayer; Colleen A Cloud; Mingli Li; Gina Scurti; Mohamed L Salem; Michelle H Nelson; Melanie B Thomas; Chrystal M Paulos; Andres M Salazar; Michael I Nishimura; Mark P Rubinstein; Zihai Li; David J Cole Journal: J Hematol Oncol Date: 2017-04-07 Impact factor: 17.388
Authors: R Curtis Bird; Patricia DeInnocentes; Allison E Church Bird; Farruk M Lutful Kabir; E Gisela Martinez-Romero; Annette N Smith; Bruce F Smith Journal: J Vet Sci Date: 2019-09 Impact factor: 1.672