Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Vaccines

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

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.

Centre Hospitalier Universitaire Vaudois

Associate Physician

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Anti-Infective Agents

Immunomodulating Agents

Interferons

Antiviral Agents

Subjects will be treated with the SV-BR-1-GM regimen in combination with retifanlimab with cycles every 3 weeks

Subjects will be treated with the SV-BR-1-GM regimen in combination with retifanlimab as follows:

Cycle 1: SV-BR-1-GM only Cycle 2: resume retifanlimab on Day 2±1 Cycle 3 and beyond: retifanlimab can be administered on Day -2, Day 0, 1, 2, or 3.

SV-BR-1-GM inoculation intradermally at 4 sites.

SV-BR-1-GM

Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation.

Post-inoculation low dose Interferon into the vaccination sites \~2 days after SV-BR-1-GM inoculation.

Interferon Inoculation

retifanlimab 375mg administered as an intravenous infusion over 30-60 minutes every 3 weeks per randomization

retifanlimab

George E Peoples, MD, FACS

This is an open-label, phase I/II double arm study of the SV-BR-1-GM regimen in combination with retifanlimab in patients with metastatic or locally recurrent breast cancer who have failed standard therapy.

Patients will receive the SV-BR-1-GM regimen with combination immunotherapy. There will be an initial evaluation of the combination of the SV-BR-1-GM regimen with retifanlimab every 3 weeks. If this is found to be safe and well tolerated in a cohort of at least 12 patients (dose-limiting toxicities (DLTs) in less than 30% of the patients evaluated), then an expansion cohort of up to 24 patients will be treated with that combination. These will be randomized to two regimens differing in the timing of checkpoint inhibitor administration.

This is an open-label, phase I/II double arm study of the SV-BR-1-GM regimen in combination with retifanlimab in patients with metastatic or locally recurrent breast cancer who have failed standard therapy.

Patients will receive the SV-BR-1-GM regimen with combination immunotherapy. There will be an initial evaluation of the combination of the SV-BR-1-GM regimen with retifanlimab every 3 weeks. If this is found to be safe and well tolerated in a cohort of at least 12 patients (dose-limiting toxicities (DLTs) in less than 30% of the patients evaluated), then an expansion cohort of up to 24 patients will be treated with that combination. These will be randomized to two regimens differing in the timing of retifanlimab administration as noted below.

The SV-BR-1-GM regimen consists of:

* Pre- SV-BR-1-GM cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation
* SV-BR-1-GM inoculation on day 0
* Interferon - at the inoculation sites 2 (±1) day post-SV-BR-1-GM

Combination therapy with retifanlimab (anti-PD-1) will be given per one of two randomized treatment arms as follows:

The SV-BR-1-GM regimen with retifanlimab will be administered every 3 weeks (± 3 days), except when approved by the Investigator in consultation with the Medical Monitor. Note that hormonal therapy (e.g., aromatase inhibitors) is permitted if ongoing, but may be added while the patient is on this study only with the Medical Monitor's approval (e.g. for hormone receptor positive patients who are deriving clinical benefit but have not achieved a CR after \>6 cycles of therapy).

Following the initial cohort, an expansion cohort of 24 patients will be randomized 1:1 into two arms with differences in initial treatment sequences: original sequence and alternative sequence. The original sequence arm will receive treatment in the same schedule as the initial cohort. Subjects in the alternative sequence will skip retifanlimab in Cycle 1, and resume retifanlimab on Day 2±1 at Cycle 2. Starting Cycle 3, retifanlimab can be administered either on Day -2/-3, Day 0 or Day 2±1. Patients will be screened to ensure they fulfill the enrollment criteria. Screening must be performed within 30 days of initiating therapy. Imaging studies must be performed within 30 days of initiating therapy for the initial 12 patients, and within 14 days for the expansion cohort (randomized portion), unless approved by the Sponsor. For subjects in expansion cohort participating in the substudy, the CD8 attenuation CT scan cannot be used for the baseline image. However, patients can be immediately scanned after the low dose attenuation scan. In the expansion cohort randomized portion of the trial, imaging must be performed within 14 days of the start of study treatment. Patients will be evaluated every 3 weeks during the study, including all safety assessments. Imaging studies will be performed every 8-12 weeks during study participation.

Pharmacodynamic assessments, including evaluation of the immune response to SV-BR-1-GM will also be performed during screening visit (substudy only), during Cycle 1, every 8-12 weeks and End of Treatment. Subsequent periodic assessments will be every 8-12 weeks from the first periodic assessment. Patients who develop progressive disease may remain on treatment for up to 6 weeks to obtain a confirmatory scan per iRECIST; or as long as the Investigator feels they are deriving clinical benefit with Medical Monitor approval. For patients who come off treatment, a final assessment will be carried out 2-4 weeks following the last dose of SV-BR-1-GM, including all safety assessments. Off-treatment subjects will continue to be followed for survival analysis every 3 months (e.g., by phone call) for at least 5 years or until death.

For the CD8 ImmunoPET sub-study, ten (10) patients will be recruited from select invited sites only, and will undergo CD8 ImmunoPET evaluation at baseline and following 3 cycles of SV-BR-1-GM therapy.

Combination Study of SV-BR-1-GM With Retifanlimab

A Phase I/II Study of the SV-BR-1-GM Regimen in Metastatic or Locally Recurrent Breast Cancer Patients in Combination With Retifanlimab

To evaluate the safety of SV-BR-1-GM as assessed by:

o Adverse Events (AEs), including Serious Adverse Events (SAEs)

To evaluate the safety of SV-BR-1-GM as assessed by:

o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters

To evaluate the safety of SV-BR-1-GM as assessed by:

o Electrocardiograms (ECG) with measurement of the QT interval

Tumor response as assessed by:

o Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per RECIST 1.1

Tumor response as assessed by:

o Non-progressive rate, defined as CR, PR or stable disease (SD) per iRECIST

Tumor response as assessed by:

o Duration of response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Combination Study of SV-BR-1-GM With Retifanlimab	NCT03328026	Breast Cancer Breast Neoplasm Metastatic Brea... Breast Cancer M...	SV-BR-1-GM Low dose cyclop... Interferon Inoc... retifanlimab	18 Years -	BriaCell Therapeutics Corporation

Spots Global Cancer Trial Database for low dose cyclophosphamide