Modified Immune Cells (TAG72-CAR T Cells) for the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer

Phase 1

Recruiting

• Conditions: Platinum-Resistant Ovarian Carcinoma
• Interventions: Biological: Chimeric Antigen Receptor T-cells; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT05225363
• Lead Sponsor: City of Hope Medical Center

Brief Summary

This phase I trial tests the safety, side effects, and best dose of TAG72-chimeric antigen receptor (CAR) T cells in treating patients with epithelial ovarian cancer that remains despite treatment with platinum therapy (platinum resistant). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize TAG72, a protein on the surface of tumor cells. These TAG72-specific T cells may help the body's immune system identify and kill TAG72+ cancer cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of TAG72-CAR T cells in participants with recurrent epithelial ovarian cancer (EOC).

II To determine the maximum tolerated dose (MTD). III. To identify the recommended phase 2 dose (RP2D).

SECONDARY OBJECTIVES:

I. Persistence of CAR T cells in blood and peritoneal cavity pre- and 28 days post-infusion.

II. Response based on Immune-Related Response Criteria (irRC). III. Estimate the 6 month progression free survival rate. IV. Estimate median overall survival. V. TAG72 expression on tumor cells by immunohistochemistry (IHC) and/or flow cytometry; VI. Describe the serum cytokine profile pre- and post-CAR T cell infusion to assess potential cytokine release syndrome (CRS) toxicity and CAR T cell effector function.

EXPLORATORY OBJECTIVES:

I. Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post- therapy: analysis will include CD4:CD8 ratios, differentiation status (CD62L, CD27, CD45 RA/RO), and exhaustion markers (PD1, Tim3, LAG3), trafficking (CCR7, alpha4beta7), proliferation markers (ki67) and effector functions (cytotoxicity, Th1/Th2 cytokines, and CD107a degranulation) on endogenous and CAR+ T cells.

II. Phenotype of tumor-infiltrating lymphocytes (TILs). III. Gene expression (by RNA-seq) of circulating tumor cells (CTCs). IV. Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood by whole exome sequencing.

V. CAR immunogenicity based on the presence of anti-TAG72 CAR antibodies or T cell mediated immune responses.

OUTLINE: This is a dose-escalation study of TAG72-CAR T cells.

Patients receive fludarabine intravenously (IV) and cyclophosphamide IV on days -5 to -3. Patients receive TAG72-CAR T cells IP on day 0.

After completion of study treatment, patients are followed up at 1, 7, 14, 21, 28, 60 and 90 days, 6, 9, and 12 months, then for up to 15 years.

Study Timeline

• Study First Submitted: 2021-12-08
• Study First Submitted QC: 2022-01-26
• Study First Posted: 2022-02-04
• Study Start: 2022-05-05
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-26
• Last Update Posted: 2025-07-01
• Primary Completion: 2026-10-05
• Study Completion: 2027-06-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 33

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (TAG72-CAR T cells)	Chimeric Antigen Receptor T-cells	Patients receive fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive TAG72-CAR T cells IP on day 0.
Treatment (TAG72-CAR T cells)	Fludarabine	Patients receive fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive TAG72-CAR T cells IP on day 0.
Treatment (TAG72-CAR T cells)	Cyclophosphamide	Patients receive fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive TAG72-CAR T cells IP on day 0.

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (DLTs)	Up to 28 days	Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.
Incidence of adverse events	Up to 1 year post treatment	Adverse Events are graded using NCI CTCAE v.5.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 1 year post treatment	Defined as death from all causes from first treatment date (either lymphodepletion or CAR T cell infusion, as applicable. Kaplan Meier methods will be used to estimate median OS, and graph the results.
Response (iRECIST)	Up to 1 year post treatment	Assessed based on Immune-Related Response Criteria. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.
Progression-free survival (PFS)	Up to 6 months post treatment	Defined as survival without biochemical (CA125) or radiographic evidence of disease progression or relapse from first treatment date (either lymphodepletion or CAR T cell infusion, as applicable). Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.
Serum cytokine profile	Up to 1 year post treatment	Serum cytokine profile before and after CAR T cell infusion: to assess potential cytokine release syndrome (CRS) toxicity and CAR T cell effector function, sequential serum samples will be analyzed for Th1/Th2 cytokines (e.g., IL-12, IFNgamma, TNFalpha, IL-10, IL-4, IL-5) by bead array
Expansion of CAR T cells	Up to 1 year post treatment	Max log10 copies/ug of genomic DNA
Persistence of CAR T cells	Up to 28 days post treatment	Defined as CAR T cells \> 0.1% of total CD3 cells by flow-cytometry.

Trial Locations

Locations (1)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States