Intensive Locoregional Chemoimmunotherapy, Intradermal Autologous Alpha-DC1 Vaccines, and Systemic Pembrolizumab for Advanced-Stage Ovarian Cancer

NCT07634094 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 25-166
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This trial proposes to evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) in the primary neoadjuvant setting. It was previously determined the tolerable dose of IPC-CKM. This study will add intradermal (ID) autologous αDC1 vaccines (known to be nontoxic) to the tolerable IPC-CKM regimen and systemic Keytruda (pembrolizumab). To optimize the pattern of immunity, all patients will also receive oral celecoxib (COX2 inhibitor).

Conditions

Ovarian Cancer

Keywords

myeloid-suppressor cell (MDSC); T regulatory cells; COX2 inhibitor; Autologous Alpha-DC1 Vaccine

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT)

  Proportion of patients in the safety cohort (chemoimmunotherapy combined with the αDC1 vaccine) experiencing a dose-limiting toxicity (DLT). A DLT will be any adverse event that is at least possibly related to the study treatment and prevents surgery or delays surgery by more than 4 weeks, or that prevents the initiation of the next cycle of treatment on schedule due to toxicity in the prior cycle. The DLT period will be 2 cycles of treatment.

  Up to 2 months

• Complete Pathologic Response (pCR)

  Percentage of patients who show no detectable cancer (cells) in tissue samples after neoadjuvant treatment as assessed at the time of the interval debulking procedure. Per RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in SLD compared to baseline, confirmed on a follow-up scan.

  Up to 5 years

Secondary Outcomes (5)

• Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 14 months

• 12-month Progression-free Survival (PFS)

  At 12 months

• 18-month Progression-free Survival (PFS)

  At 18 months

• Progression-free Survival (PFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 7 years

Study Arms (2)

Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

EXPERIMENTAL

Drug: Paclitaxel; Drug: Cisplatin; Drug: Bioferon; Drug: Rintatolimod; Drug: Pembrolizumab; Drug: Celecoxib; Procedure: Debulking Procedure

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib

EXPERIMENTAL

Drug: Paclitaxel; Drug: Cisplatin; Drug: Bioferon; Drug: Rintatolimod; Biological: αDC1 Vaccine; Drug: Pembrolizumab; Drug: Celecoxib; Procedure: Debulking Procedure

Interventions

Paclitaxel DRUG

A chemotherapy for cancer patients that interferes structures that help move chromosomes during cell division, thus stabilizing these structures to prevents cancer cells from dividing and ultimately causing them to die. Dose: 175 mg/m\^2 IV on D1 each cycle during neoadjuvant and adjuvant periods.

Also known as: Taxol, taxane

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

Cisplatin DRUG

An alkylating agent that contains platinum, which binds to DNA in cancer cells, causing cross-links that prevent DNA replication and repair, leading to cell death, particularly in rapidly dividing cancer cells. Dose: 75 mg/m\^2 IP / 1 hour on D1 of each cycle during neoadjuvant and adjuvant treatment periods.

Also known as: Platinol®

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

Bioferon DRUG

Inhibits replication of a wide range of RNA and DNA viruses and exerts antiproliferative effects on malignant cells. It suppresses antibody formation through an effect on B-lymphocytes and inhibits onset of delayed hypersensitivity. Dose:6 milli on units/100 mL IP over 30-60 minutes on D2 of each cycle during neoadjuvant and adjuvant treatment. D1 during maintenance treatment periods.

Also known as: (Interferon Alfa)-2a

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

Rintatolimod DRUG

A synthetic double-stranded RNA that selectively activates Toll-like Receptor 3 (TLR3), triggering antiviral and immunomodulatory responses, priming the immune system without causing excessive inflammation. Dose: 200 mg IP over 1-2 hours on D2 of each cycle during the neoadjuvant and adjuvant treatment periods. D1 during maintenance treatment periods

Also known as: Ampligen®

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

αDC1 Vaccine BIOLOGICAL

Autologous tumor-loaded alpha-DC1 vaccine is the new type of dendritic cell vaccine developed by our group, are the serum-free, clinically-applicable version of type-1 polarized DCs, combining a fully-mature phenotype and high expression of co-stimulatory molecules with an elevated, rather than exhausted, ability to produce IL-12p70. Dose: 6 million dendritic cells (reduced or omitted if insufficient vaccine material), ID injection on rotating sides of lower extremities on D2 each cycle during the neoadjuvant (not C1) and adjuvant treatment periods. D1 of each cycle during maintenance period.

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib

Pembrolizumab DRUG

Humanized monoclonal antibody and a PD-1 inhibitor used in cancer immunotherapy that differs from chemotherapy as it does not directly kill cancer cells but stimulates the immune system, particularly T-cells, to recognize and attack cancer cells more effectively. Dose: 200 mg IV / 30 minutes on D2 of each cycle during neoadjuvant treatment period (none last neoadjuvant cycle), then optional on D2 for adjuvant treatment cycles, and on D1 of maintenance cycles

Also known as: Keytruda®

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

Celecoxib DRUG

A COX-2 inhibitor in the class of nonsteroidal anti-inflammatory drugs (NSAIDs) that specifically target the cyclooxygenase-2 (COX-2) enzyme, which plays a key role in inflammation Dose: 200mg/day, orally twice a day for days 1-5 and once a day for days 6-21 of neoadjuvant and adjuvant treatment cycles, and then twice a day on D1 and once a day for days 2-21 for maintenance cycles

Also known as: Celebrex®

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

Debulking Procedure PROCEDURE

A surgical procedure designed to remove the majority of cancerous tumors when complete removal may not be feasible, with the goal of reducing tumor burden, making follow-up treatments like chemotherapy or radiation more effective. Surgery occurs in between the neoadjuvant and adjuvant treatment periods.

Also known as: cytoreductive surgery

Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib; Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have advanced stage (III-IV) epithelial carcinoma or carcinosarcoma of ovarian, tubal or peritoneal origin.
• a. Histologic documentation of the original primary tumor is required via a pathology report.
• Patients must be eligible for cancer-related definitive therapy with neoadjuvant chemotherapy.
• Patients must be chemo-naive and receiving therapy in primary first-line neoadjuvant setting.
• Patients must have ECOG performance of 0-1.
• Patients must be reasonable candidate for interval debulking surgery as well as for IP platinum-based combination chemotherapy regimen, with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal disease or bowel obstruction.
• At least one lesion must be considered to be large enough for biopsy and resection to yield greater than 2 grams of tumor for tumor loading of αDC1's and immunoassays at the discretion of the treating investigator and/or surgeon.
• Patients must have measurable disease per iRECIST criteria.
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry, during the course of the study, and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
• Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
• a. Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
• Patients must be willing to undergo leukapheresis.
• Patients must be willing to adhere to protocol requirements.
• Patients must have adequate:
• Bone marrow function:

You may not qualify if:

• Patients with sarcoma.
• Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).
• Patients with a known allergy to cisplatin or taxane chemotherapy. Patients with carboplatin allergy may be included if they tolerate a test dose of IV cisplatin given in monitored floor conditions. Patients who are allergic to paclitaxel can be alternatively treated with abraxane.
• Patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.
• a. Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained.
• Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies.
• Patients with uncontrolled diseases other than cancer will be excluded.
• Patients who have contraindications to the use of NSAID's like chronic renal failure, coronary artery disease, or bleeding ulcers.
• Patients who have contraindications to the use of interferon α-2b (Bioferon), including hypersensitivity to interferon-α or any component of the product, autoimmune hepatitis, and decompensated liver disease.
• Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with no peritoneal disease.
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Patients with previous pelvic radiation therapy.

Sponsors & Collaborators

• Kalinski, Pawel, MD, PhD: lead
• AIM ImmunoTech Inc.: collaborator
• Northwest Biotherapeutics: collaborator

Study Sites (1)

UMPC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Paclitaxel; taxane; Cisplatin; Interferon alpha-2; poly(I).poly(c12,U); pembrolizumab; Celecoxib; Cytoreduction Surgical Procedures

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Surgical Procedures, Operative

Study Officials

• Robert Edwards, MD

  UPMC Magee Womens Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey Mitch, RN, BSN

CONTACT

4126412357; adamikka2@upmc.edu

Lucia M Borrasso, RN, BSN

CONTACT

4126413304; borrlm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Obstetrics, Gynecology, and Reproductive Sciences

Model Details: All drugs will be dosed on a 21-day cycle. The study will consist of 3-4 neoadjuvant treatment cycles, 2-4 adjuvant treatment cycles, and 8 optional maintenance treatment cycles, for a total of 5-16 treatment cycles. An interval debulking procedure will occur in between the neoadjuvant and adjuvant periods of study treatment. The optional maintenance treatment cycles may be included depending on available resources and the clinical opinion of the treating investigator and/or principal investigator. There is the possibility that not all drugs in the maintenance regimen will be administered (e.g. one or more drugs may be omitted, or maintenance cycles may be omitted all together). No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the subject's malignancy.

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 8, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)