Faculty Opinions recommendation of A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma.

2639 Background: We developed a HER2 targeting autologous dendritic cell (DC) vaccine transduced with an adenovirus expressing the extracellular and transmembrane domains of HER2 (AdHER2). In mice, the homologous vaccine cured virtually all mice with established or metastatic tumors. Protection was dependent on antibodies against HER2 that inhibited phosphorylation, but was ADCC independent. We translated these findings into a clinical trial. Methods: This is an open-label, phase I study in patients with 1) metastatic cancer that progressed after ≥ 1 standard therapies, or 2) history of high risk bladder cancer with definitive treatment, whose tumor is HER2 immunohistochemistry (IHC) score ≥ 1+ or FISH HER2/CEP17 ratio ≥ 1.8. Part 1 of the study enrolled patients naïve to HER2-directed therapies and Part 2 enrolled patients who progressed with ≥ 1 anti-HER2 therapy. Results: In Part 1, the lowest dose level (5E+6 viable DCs, N=7, 2 inevaluable) showed no benefit. At the second and third dose level (10E+6 and 20E+6; N=7 and N=4; 0 and 1 inevaluable in each), 1 CR (ovarian), 1 PR (stomach), and 3 SD (1 ovarian carcinosarcoma and 2 colon) were observed. Two bladder cancer patients who received vaccine as an adjuvant did not recur for +24 and +36 month each. In Part 2 (N=6, 2 inevaluable), 1 male breast cancer patient showed SD. Response assessed by Modified Immune Related Response Criteria is summarized in the Table. Injection-site reactions occurred in all patients and were self-limited. Echo, EKG and troponin follow up to 2 years showed no cardiac toxicity. Dose-expansion cohort (40E+6) is enrolling. Conclusions: We have translated a cancer vaccine from mice to a clinical trial. Preliminary results of a phase I trial of an autologous AdHER2 DC vaccine show potential clinical benefit in select patients with HER2 expressing tumors with no cardiac toxicity. Clinical trial information: NCT01730118. [Table: see text]

Download Full-text

EPCT-13. CMV PP65 RNA-PULSED DENDRITIC CELL VACCINES FOR PEDIATRIC GLIOBLASTOMA AND MEDULLOBLASTOMA: PHASE I TRIAL RESULTS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.136 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii306-iii306

Author(s):

Daniel Landi ◽

Gary Archer ◽

Timothy Driscoll ◽

Eric Lipp ◽

Bridget Archambault ◽

...

Keyword(s):

Dendritic Cell ◽

Phase I ◽

Malignant Glioma ◽

Phase I Trial ◽

Active Immunization ◽

Monocyte Differentiation ◽

Dendritic Cell Vaccines ◽

Dc Vaccines ◽

Subsequent Phase ◽

Children And Young Adults

Abstract BACKGROUND Recurrent medulloblastoma and malignant glioma are lethal tumors that are virtually incurable. The cytomegalovirus (CMV) antigen pp65 is ubiquitously expressed on medulloblastoma and malignant glioma but not on healthy brain. We evaluated autologous CMV pp65 RNA-pulsed dendritic cell (DC) vaccines in children and young adults in a phase I trial. METHODS Circulating monocytes were harvested using leukapheresis, differentiated into DCs, matured, and pulsed with pp65 RNA using electroporation. DCs were packaged into vaccines (2x107DC/vaccine) and administered intradermally following tetanus-diphtheria toxoid site preconditioning every 2 weeks x3, then monthly. The primary objectives of the study were to establish the feasibility of generating at least 3 vaccines and safety. An exploratory objective was to evaluate the ability of vaccination to create and enhance patient pp65-specific T cell responses. RESULTS Eleven patients were enrolled with medulloblastoma (n=3) or glioblastoma (n=8). Ages ranged from 9–30 years old (mean 15.5y). Ten of 11 patients (91%) generated at least 3 vaccines (mean 6.2). Eight patients received at least 3 vaccines. To date, 4 patients have received all generated vaccines without progression, 4 patients have progressed, and 2 patients are still receiving vaccines. There have not been any severe adverse events probably or definitely related to vaccines. More mature data will be presented at ISPNO. CONCLUSIONS Leukapheresis and monocyte differentiation is a feasible strategy for generating adequate DCs for active immunization in children with malignant brain tumors. CMV pp65 RNA-pulsed DCs are well-tolerated and immunogenic. Efficacy endpoints will be evaluated in a subsequent phase II trial.

Download Full-text