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Cyclophosphamide

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Alkylating Agents

In arm A, patients will receive PEP-DC1 vaccine in combination with low dose cyclophosphamide.

In arm B, patients will receive first, the OC-DC vaccine in combination with low dose cyclophosphamide, then PEP-DC2 vaccine in combination with low dose cyclophosphamide. Finally, patients will be vaccinated with the personalized PEP-DC2 to continue maintenance vaccination.

PEP-DC1 vaccine comprises autologous dendritic cells pulsed with personalized peptides detected or predicted a priori (using our current integrated antigen identification methodologies).

PEP-DC1

OC-DC vaccine is an autologous dendritic cell vaccine loaded with autologous oxidized tumor lysate.

OC-DC

PEP-DC2 comprises autologous dendritic cells pulsed with the peptides detected or predicted after vaccination with OC-DC.

PEP-DC2

Cyclophosphamide administered on D1 of each cycle, the day prior to each vaccination (Vx) at a dose of 200 mg/m2 intravenously (i.v.)

Low dose cyclophosphamide

Lana Kandalaft, Pharm D, PhD

Apostolos Sarivalasis, MD

Single center, phase I/II randomized 2-arm study, evaluating two different vaccination regimens combined with low-dose cyclophosphamide in patients with advanced high grade serous ovarian carcinoma (HGSOC):

* Arm A patients will be vaccinated with a personalized peptide vaccine comprised of autologous monocyte-derived dendritic cells (moDC) loaded with patient-specific peptides (PEP-DC1 vaccine) identified a priori at screening (8 patients);
* Arm B patients will be vaccinated with a personalized tumor lysate vaccine comprising autologous moDC loaded with patient-specific autologous oxidized tumor lysate (OC-DC vaccine), followed by PEP-DC2 vaccine comprised of autologous moDC loaded with up to 10 patient-specific peptides identified midway through OC-DC vaccination (8 patients).

In both arms, patients will receive a low dose cyclophosphamide the day before vaccination. Patients will be vaccinated after the end of adjuvant platinum-based chemotherapy, until vaccine exhaustion, disease recurrence, major toxicity or patient withdrawal, whichever is earlier.

This will be a single center, Phase I/II randomized, two-arm, open-label study to evaluate immunogenicity, safety, and feasibility of two different vaccination regimens combined with low-dose cyclophosphamide in patients with surgically resected, advanced HGSOC. Patients with HGSOC at International Federation of Gynecology and Obstetrics (FIGO) stage III or IV who completed either primary debulking surgery (PDS) or interval debulking surgery (IDS) without residual disease (R0) and who have received at least 6 cycles of adjuvant standard of care (SOC) platinum-based chemotherapy after PDS, or 3 cycles of platinum-based perioperative chemotherapy within an IDS will be eligible for this protocol. A total of 16 patients (8 patients in each arm) will be randomized 1:1 as follows:

* In arm A, patients will receive PEP-DC1 vaccine comprising autologous dendritic cells pulsed with personalized peptides detected or predicted a priori (using our current integrated antigen identification methodologies).
* In arm B, patients will receive first, the OC-DC vaccine, an autologous dendritic cell vaccine loaded with autologous oxidized tumor lysate. Then, tumor antigens specifically recognized by the patients' immune response induced by OC-DC vaccination will be identified/predicted using integrated methodologies to enable production of PEP-DC2 vaccine (autologous dendritic cells pulsed with the peptides detected or predicted after vaccination with OC-DC). Finally, patients will be vaccinated with the personalized PEP-DC2 to continue maintenance vaccination.

In both arms, vaccines will be administered to the patients in combination with low dose cyclophosphamide the day before vaccination. Patients will be vaccinated in the adjuvant setting, with first vaccine injected no more than 18 weeks after the end of SOC platinum-based chemotherapy. Patients will be vaccinated until vaccine exhaustion (which may happen any time after dose 6), disease recurrence, major toxicity or patient withdrawal, whichever is earlier.

PEP-DC and OC-DC Vaccine in High Grade Serous Ovarian Carcinoma

Phase I/II Study to Test the Immunogenicity, Feasibility, and Safety of Autologous PEP-DC Vaccine vs. Autologous OC-DC Vaccine Followed by PEP-DC Vaccine, in Combination With Low-dose Cyclophosphamide, in Patients With Advanced HGSOC

The number of personalized tumor antigen (PTAs) ranked as Top 100 will be identified for each patient before and after treatment and the difference will be compared between the two arms at least at two time-points, first at the end of the 3rd cycle (C3W3), and second, at end of treatment (EOT) visit (if possible at C6W4-W6 also). Specifically, an immunogenicity scoring will be determined as follows: for each of the 100 pre-determined top PTAs, a score will indicate how many peptides either become newly detected (shift from undetectable to detectable) or have a magnitude (frequency of T-cell directed against the epitope) increased by ≥ 2 fold.

Feasibility of producing and administering vaccines will be evaluated by:

i) the number of patients for whom vaccine is produced successfully (defined as production and quality control release of at least 6 doses of PEP-DC1 vaccine for Arm A patients, and at least 6 doses of OC-DC vaccine and 6 doses of PEP-DC2 vaccine for Arm B patients) and ii) the number of patients who receive at least one vaccine dose among the randomized patients.

Feasibility is considered as achieved if within each arm, at least 50% of the randomized subjects comply with these criteria.

Collection of adverse events and serious adverse events, and treatment limiting toxicities

Will be evaluated in the 2 arms. TTP is the time from randomization to date of first documented objective tumor progression according to RECIST 1.1 criteria and cancer antigen (CA) 125 Gynecologic Cancer InterGroup (GCIG) criteria.

DFS is defined as the time from randomization to date of first documented objective tumor recurrence according to RECIST 1.1 and CA 125 GCIG criteria, or, death due to any cause or last patient contact in which the patient was determined to be disease-free.

Will be assessed in both arms. OS is defined as the time from randomization to date of death due to any cause, or last patient contact.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PEP-DC and OC-DC Vaccine in High Grade Serous Ovarian Carcinoma	NCT05714306	Ovarian Carcino...	PEP-DC1 OC-DC PEP-DC2 Low dose cyclop...	18 Years -	Centre Hospitalier Universitaire Vaudois
PEP-DC and OC-DC Vaccine in High Grade Serous Ovarian Carcinoma	NCT05714306	Ovarian Carcino...	PEP-DC1 OC-DC PEP-DC2 Low dose cyclop...	18 Years -	Centre Hospitalier Universitaire Vaudois

Spots Global Cancer Trial Database for advanced high grade serous ovarian carcinoma