An open label, phase 1 study to evaluate the safety, feasibility and immunogenicity of an allogeneic, cell-based vaccine (DCP-001) in high grade serous ovarian cancer patients after primary treatment

Ovarian cancer (OC) is the leading cause of death from gynecological
malignancies with a 5-year survival of no more than 40%. Current standard
treatment (surgery and chemotherapy) is initially effective, but almost all
patients suffer from chemotherapy-resistant relapse. After cytoreductive
surgery (complete/suboptimal), most patients remain in a state of microscopic
minimal residual disease until relapse.
Recently maintenance therapy has been introduced for these patients with the
approval of poly adenosine diphosphate ribose polymerase inhibitors (PARPi) for
BReast CAncer gene (BRCA) germline mutated OC patients. PARPi treatment showed
beneficial clinical effect in large trials by improving progression free
survival (PFS) and overall survival (OS) in OC patients with deleterious
germline BRCA mutations. Approximately, 10-15% of epithelial ovarian cancer
patients carry the germline BRCA1/2 mutation, the highest prevalence (20%) is
found in the high grade serious subtype. However, it still leaves the majority
of OC patients without an effective maintenance therapy. Therefore, new
approaches that improve therapeutic outcome for OC patients are urgently
needed.
Here, we propose a novel immunotherapeutic approach using an allogeneic
cell-based vaccine (DCP-001), consisting of cells expressing common
tumor-associated antigens, expressed by OC as well, and having characteristics
of dendritic cells (DC), as a novel maintenance therapy in OC. Dendritic cells
are professional antigen-presenting cells (APCs) and exquisitely suited to
induce anti-tumor immune responses.
Clinical activity of DC-based immunotherapy in OC was recently demonstrated by
Cibula et al. (2018) showing an improved OS in relapsed platinum-sensitive OC
patients treated with second line chemotherapy (carboplatin/gemcitabine) in
combination with DC-based immunotherapy (DCVAC/OvCa) compared to chemotherapy
alone. In another study design, DCVAC/OvCa was administered sequentially as
maintenance therapy after completing SoC treatment and demonstrated an improved
PFS in OC patients. Administration of a vaccine after successful initial
treatment has the potential advantage of eradicating residual tumor cells,
providing optimal conditions for the immune system to prevent clinical relapse.
For the current protocol, we propose the use of a maintenance therapy with the
allogeneic cell-based vaccine, DCP-001.
This novel vaccine was developed from an acute myeloid leukemia (AML)-derived
cell line that uniquely combines the positive features of allogeneic DC
vaccines and expression of multiple tumor associated antigens. Vaccination with
DCP-001 in 12 post-remission AML patients prolonged minimal residual disease
status and was associated with improved PFS and systemic immunogenicity.
Administration of the vaccine was associated with only limited side-effects
like fever, injection site reactions, adenopathy, and fatigue. A phase II trial
in AML is currently ongoing.
Importantly, the tumor associated antigens (TAAs) expressed by DCP-001 are
shared across tumor types, most notably ovarian cancer. These antigens include,
but are not limited to, the hallmark OC antigens: WT-1, MUC-1, Survivin, and
PRAME. In addition, immune monitoring results from a completed phase I clinical
study in AML showed that DCP-001 vaccination also induced immune responses
towards TAAs which are not directly expressed by DCP-001 cells itself, like
NY-ESO and MAGE-A3, which are two other dominant TAAs in ovarian cancer.
Accordingly, pre-clinical studies of DCP-001 with isolated peripheral blood
cells of OC patients resulted in potent vaccine-induced T cell responses in
general and also specifically against certain OC cell lines. On top of that,
DCP-001, when used as relapse vaccine in a humanized mouse model of OC, was
capable to suppress tumor growth and lead to tumor regressions.
Taken together, these data support the evaluation of DCP-001 as relapse vaccine
in high grade serous ovarian cancer (HGSOC) patients.

This study has been transitioned to CTIS with ID 2024-516781-10-00 check the CTIS register for the current data.

Primary objective:
• Systemic immunogenicity of the DCP-001 vaccination in high grade serous
ovarian (HGSOC) cancer patients.

This is a first phase I study in HGSOC patients with primary disease eligible
for SoC treatment with either complete or optimal primary cytoreductive surgery
followed by 6 cycles of adjuvant chemotherapy (carboplatin/paclitaxel) or 3
cycles of neoadjuvant chemotherapy (carboplatin/paclitaxel) followed by
complete or optimal cytoreductive interval surgery and 3 additional cycles
carboplatin/paclitaxel.
In the current study, DCP-001 vaccinations will be scheduled after SoC
treatment.
Six doses (4 vaccinations and 2 boosters) of DCP-001 vaccine will be
administered to induce an anti-tumor immune response between 6 and 24 weeks
after the last cycle carboplatin/paclitaxel. Systemic immune responses are
determined by standard immune assays using peripheral blood mononuclear cells
(PBMCs) and serum collected before, during and after vaccinations. Progression
of disease will be monitored according to standard-of-care follow-up.

Patients will receive 6 intradermal vaccinations.

Patients in this phase I pilot have received and completed SoC treatment for
HGSOC and might experience benefit from this study. The intended goal of the
study is to induce a specific anti-cancer immune response. When immunity is
induced, the immunotherapy may even prevent recurrence of the disease.
Six vaccinations by intradermal injection are performed with additional vena
punctures for immune monitoring. Visits and study related blood collections are
aligned to and combined with SoC procedures as much as possible.
Initial clinical data from DCP-001 studies demonstrates that a dosage of at
least 25 million cells per vaccination is safe and sufficient for induction of
a potent immune response with only limited side-effects like fever, injection
site reactions, adenopathy, and fatigue. We will monitor the safety and
toxicity of this cancer vaccine in the current trial, using GCP guidelines.
Toxicity will be graded according to the NCI CTCAE Version 5.0.