Standard treatment of primary ovarian epithelial cancer has improved, but 5-year survival is only about 40% for the cohort of patients who present with stage 3 or 4 disease. Adjunctive therapy with patient-specific vaccines may improve outcomes by enhancing each patient's anti-cancer immune response. A multi-institutional, double- blinded randomized phase II clinical trial was designed with a primary objective of a 50% reduction in the risk of death compared to the control arm. Key eligibility criteria are: (1) primary diagnosis of stage 3 or 4 ovary epithelial cancer, (2) successful cell culture of ovarian cancer cells, (3) successful monocyte collection by leukapheresis, and (4) ECOG of 0 or 1 at the time of randomization. After completing primary systemic therapy, patients are stratified based on whether they have any residual evidence of disease and then randomized 2:1 to vaccine or control arms. Randomization occurs about 7 months after initial surgery. In the active arm IL-4 and GM-CSF are used to differentiate monocytes into dendritic cells (DC) which are incubated with the lysate of cultured ovary cancer cells as the source of autologous tumor antigens (ATA) to produce each patient-specific DC-ATA vaccine. Patients in the control arm receive cryopreserved autologous monocytes from their leukapheresis product. Each dose is admixed with 500 mcg GM-CSF at the time of subcutaneous injections at weeks 1, 2, 3, 8, 12, 16, 20 and 24. DC-ATA may be given alone or in combination with maintenance or salvage therapies. At the time of this analysis, cell line success rate is 35/35 (100%); monocyte collection success rate is 19/20 (95%), and 2 patients required a second apheresis to get a satisfactory product. 14 patients had primary ovarian, 2 fallopian tube, and 1 primary intraperitoneal cancer. 17 of a planned 99 have been randomized. At diagnosis 15 patients had stage 3 disease and two had stage 4; 15 had no evidence of disease at the time of randomization. Primary systemic therapy was adjuvant for 7 and neoadjuvant for 10. Ages of the randomized patients range from 39 to 80 years with a median of 61 years. ECOG status was 0 for 11 subjects, and 1 for 6 subjects. 13 patients have started treatment and received 92 injections; 9 have received all 8 doses and only 2 have stopped before 8 doses. No patient has discontinued treatment because of toxicity, but 1 patient was hospitalized after the 8th dose for refractory urticaria that resolved after high-dose corticosteroids followed by slow tapering. This patient-specific DC-ATA immunotherapy approach is feasible in patients with primary advanced ovarian cancer. The clinical trial is continuing as planned. [Clinicaltrials.gov NCT02033616] Citation Format: Lisa N. Abaid, Bradley R. Corr, James R. Mason, Richard L. Friedman, Ramez N. Eskander, Candace Hsieh, Chris J. Langford, Krystal Carta, Adrienne M. Wang, James A. Langford, Gabriel I. Nistor, Robert O. Dillman. Patient-specific dendritic cell vaccines with tumor antigens from self-renewing autologous tumor cells in the treatment of primary advanced ovarian cancer: A multi-institutional phase II clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT189.

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Standard treatment of primary glioblastoma (GBM) is associated with poor survival. Adjunctive therapy with patient-specific vaccines may improve outcomes by inducing or enhancing each patient's anti-GBM immune response. A multi-institutional phase II clinical trial was designed with a primary objective of 75% survival 15 months after intent-to-treat enrollment. Key eligibility criteria were: (1) primary GBM diagnosis, (2) age < 70 years at time of tumor resection, (3) successful cell culture of GBM cells in serum-free media, (4) successful monocyte collection by leukapheresis, and (5) KPS > 70 after recovery from surgery. IL-4 and GM-CSF were used to generate dendritic cells (DC) from monocytes. DC were incubated with autologous tumor antigens (ATA) from the lysate of cultured GBM cells to produce each patient-specific DC-ATA vaccine. Each dose was admixed with GM-CSF at the time of subcutaneous injections at weeks 1, 2, 3, 8, 12, 16, 20 and 24. At the time of this analysis, cell line success rate is 61/63 (97%); monocyte collection success rate is 53/55 (96%), but 10 patients required a second apheresis. 50 of a planned 55 patients have enrolled after recovery from surgery, just prior to starting standard concurrent radiation therapy (RT) and temozolomide (TMZ), with intent-to-treat after recovery from RT/TMZ. The 50 patients include 36 men and 14 women; median age is 58 years with a range of 27 to 70. Average KPS is 82.8. MGMT methylation has been documented in 22% of patients and IDH mutation in 14%. 37 patients have started treatment and received 231 doses. 16 have completed all 8 doses, 7 received fewer than 8 doses, and 14 are currently undergoing treatment. No patient has discontinued treatment because of toxicity, but 20 patients have experienced 35 treatment-emergent serious adverse events including hospitalizations for falls and/or increased focal weakness (12 episodes), seizures (10 episodes), or severe headaches or visual changes (3 episodes). 6-month actual survival rate is 96% for the 28 patients at risk 6 months or longer from enrollment. Serologic analyses show that 12 of 16 patients (75%) had an increase in markers associated with Th1/NK, Th2/immunoglobulins, and Th2 hypersensitivity (eotaxins, IgE and IL17F) by week-3; 9 of 15 (60%) had a decrease in angiogenesis factors, growth factors, and tumor markers by week-8. On serial MRI scans, 7 of 13 patients (54%) have exhibited an increase in T2 (tumor) and flare (edema) for several weeks after starting DC-ATA, followed by a slow gradual decrease in both. This patient-specific DC-ATA immunotherapy approach is feasible, is associated with changes in serologic markers, and may be increasing intratumor inflammation that may be associated with on-target toxicity and efficacy. Longer follow up is needed before the survival objective can be assessed. [Clinicaltrials.gov NCT03400917] Citation Format: Daniella A. Bota, Christopher M. Duma, Santosh Kesari, David E. Piccioni, Renato V. LaRocca, Robert T. O'Donnell, Robert D. Aiken, Jose A. Carrillo, Candace Hsieh, Chris J. Langford, Krystal Carta, Adrienne M. Wang, James A. Langford, Thomas H. Taylor, Gabriel I. Nistor, Robert O. Dillman. Adjunctive treatment of primary glioblastoma with patient-specific dendritic cell vaccines pulsed with antigens from self-renewing autologous tumor cells: A phase II trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT182.

GBM standard treatment is associated with poor survival. Adjunctive therapy with patient-specific vaccines may improve outcomes by enhancing anti-GBM immune responses. A multi-institutional phase II clinical trial was designed with a primary objective of 75% survival 15 months after intent-to-treat enrollment. IL-4 and GM-CSF were used to generate dendritic cells (DC) from monocytes. DC were incubated with autologous tumor antigens (ATA) from the lysate of cultured GBM cells to produce each patient-specific DC-ATA vaccine. Each dose was admixed with 500 mcg GM-CSF at the time of subcutaneous injections at weeks 1, 2, 3, 8, 12, 16, 20 and 24. Enrollment has been completed in April 2020 (n=60). Three patients withdrew from the study prior to starting treatment leaving 57 patients for whom data is available. So far 57 patients have received 344 doses; 27 have completed all 8 doses, 11 received fewer than 8 doses at the time they discontinued treatment, 19 are currently in treatment. No patient has discontinued treatment because of toxicity. 9 pt had died and the preliminary 12 months overall survival is 74%. In a preliminary serologic analysis 12 of 16 patients (75%) had an increase in markers associated with Th1/NK, Th2/immunoglobulins, and Th2 hypersensitivity (eotaxins, IgE and IL17F) by week-3; 9 of 15 (60%) had a decrease in angiogenesis factors, growth factors, and tumor markers by week-8. Immunologic data for all 55 patients who received at least two injections will be available November 2020. This patient-specific DC-ATA immunotherapy approach is feasible, is associated with changes in serologic markers, and may be increasing intratumor inflammation that may be associated with on-target toxicity and efficacy. A interim survival analysis will be conducted in mid-October 2020, 15 months after the 28th patient was enrolled; results will be available November 2020 [Clinicaltrials.gov NCT03400917].