Study of Autologous, Metabolically Optimized, CD137+ Tumor-Infiltrating Lymphocytes Followed by Consolidative Oral Cyclophosphamide, Bevacizumab, and Pembrolizumab

NCT07720180 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 104297
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with recurrent ovarian cancer will undergo resection of a safely accessible metastatic lesion, from which tumor-infiltrating lymphocytes (TIL) will be cultured, metabolically reprogrammed for metabolic fit T cells, then selected for CD137+ activated T cells, and then expanded. This expanded TIL product will be infused following nonmyeloablative lymphodepletion chemotherapy. High-dose IL-2 will be given after TIL infusion to support the cell product expansion. Once recovered from TIL infusion, patients will start consolidative systemic therapy with oral cyclophosphamide, bevacizumab, and pembrolizumab.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT) incidence

  The proportion of DLT events will be summarized using exact binomial confidence intervals. This proportion will be calculated based on the DLT evaluable analysis set.

  12 months

• Binary patient level indicator for manufacturing success

  Defined by TIL generation \>1 x 109 followed by successful TIL infusion.

  12 months

Secondary Outcomes (3)

• Overall response rate

  12 months

• Progression free survival

  12 months

• Overall Survival

  12 months

Study Arms (1)

IL Therapy With Lymphodepletion and Consolidative Therapy

EXPERIMENTAL

Patients undergo tumor resection for collection of tumor-infiltrating lymphocytes (TIL), followed by lymphodepleting chemotherapy (fludarabine and cyclophosphamide), TIL infusion, and high-dose IL-2. After recovery, patients receive consolidative therapy with oral cyclophosphamide, bevacizumab, and pembrolizumab.

Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Fludarabine DRUG

25 mg/m2/day

IL Therapy With Lymphodepletion and Consolidative Therapy

Cyclophosphamide DRUG

60 mg/kg/day IV

IL Therapy With Lymphodepletion and Consolidative Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• STEP 1: RESECTION OF TUMOR \& INITIATION OF TIL EXPANSION Patients must fulfill all of the following criteria to be eligible for the study at the time of tumor resection and initiation of TIL expansion.
• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Female, aged 18 to 80 years.
• Patients must have recurrent epithelial ovarian cancer, all subtypes will be eligible.
• Measurable disease for target lesion(s) per RECIST prior to resection. If only one measurable lesion prior to surgery, residual disease measurable lesion must be present after resection on baseline imaging.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 to 1 and life expectancy of \> 6 months.
• Patients must have progressed on at least one prior standard of care treatment regimen for metastatic disease, may include platinum sensitive and resistant patients. Platinum sensitive disease as defined by recurrence of disease more than 6 months following a complete response to initial treatment and platinum recurrent as defined by recurrence less than 6 months after a complete response to initial treatment. If patients are 2nd line platinum sensitive, they must have progressed \< 1 year of last platinum therapy. Also, for 2nd line platinum sensitive patients that are candidates for PARP maintenance, they must have had a frontline PARP maintenance or attempt at PARP maintenance with unacceptable toxicity/intolerance. For 3rd line or more platinum sensitive patients, all platinum free intervals (PFI) are acceptable.
• a. The allowance of platinum sensitive patients is based on the high response rate and durability (Sensitive: ORR-60% DOR-11.5 mos, vs Resistant: ORR 43.3, DOR 5.5 mos) seen in the study that gave rationale for the consolidative regimen of oral cyclophosphamide, bevacizumab, pembrolizumab (Zsiros et al, 2021). As well, higher responses are observed to targeted therapies in platinum sensitive patients (mirvetuximab Plat Sens: ORR 51% vs Plat resistant: 32%), similar to platinum combination response rates and PFS. By introducing an immunotherapeutic-targeted regimen in platinum sensitive patients, it further extends the platinum free interval (PFI) increasing later platinum response potential, especially those in the 6-12 mos PFI.
• A negative pregnancy test (urine or serum) must be documented at screening for women of childbearing potential.
• A MUGA/ECHO scan (ejection fraction \> 45% is required) ≤ 6 months prior to lymphodepletion. New York Heart Association functional classification Class \<1 are required.
• Patients who have a history of ischemic heart disease, angina, or clinically significant atrial and/or ventricular arrhythmias must undergo a cardiac stress test, patients with abnormal cardiac stress test, may be considered for study if they have adequate ejection fraction (\>45%) and cardiology clearance with approval of Primary Investigator.
• Screening Pulmonary function tests should be performed for select patients (see below) with postbronchodilator values: Forced expiratory volume in 1s, (FEV1)/forced vital capacity\>70%' or FEV1\>50% of predicted normal is recommended.
• History of cigarette smoking of ≥ 20 pack-years
• Cessation of smoking withing past 2 years or still smoking

You may not qualify if:

• STEP 1: RESECTION OF TUMOR \& INITIATION OF TIL EXPANSION
• Patients who meet the following criteria will be excluded from study participation:
• Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders, or other major medical illnesses of the cardiovascular, respiratory, or immune system.
• Frontline platinum refractory patients (progression on or \<90 days from last platinum dose)
• Patients that have completed an adoptive cellular therapy regimen which included a non-myeloablative lymphodepletion strategy. Prior Bi-specific T-cell engagers are allowed if done without lymphodepletion and no grade 3 CRS/ICANs events were experienced.
• Patients testing positive for HIV titer, hepatitis B surface antigen, human T-cell leukemia-lymphoma virus (HTLV) I or II antibody, or both rapid plasma regain (RPR) and fluorescent treponemal antibody (FTA). Patients with hepatitis C antibody must have a negative (undetectable) viral load by polymerase chain reaction (PCR).
• Patients who are pregnant or nursing.
• Patients needing chronic immunosuppressive systemic steroids (\>10mg/day prednisone or equivalent).
• Patients with autoimmune diseases that require immunosuppressive medications.
• Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated.
• Patients with active untreated central nervous system metastases. Patients will be allowed with historically treated brain metastasis (treatment completed \>28 days prior to consenting to study) and they undergo MRI at screening that reveals no new or worsening brain lesions and does not require ongoing corticosteroid treatment (\>10mg/day prednisone or equivalent). Patients with leptomeningeal disease are excluded regardless of prior brain treatment response.
• Patients with a separate primary malignancy within the past 3 years (except those that did not require more than excisional curative treatment for early stage, or have been curatively treated, and in the judgement of the investigator does not pose a significant risk of recurrence, including but not limited to non-melanoma skin cancer, ductal/lobular carcinoma in situ of the breast, or superficial bladder cancer).
• Patients with recent clinical evidence of malignant bowel obstruction (small intestine or colon) in the past 60 days unless was unrelated to malignancy and surgically corrected (ex. - hernia) \>28 days prior to signing consents.
• Participants with any form of primary immunodeficiency (ex. Severe combined immunodeficiency disease or AIDS).
• Patient with history of hypersensitivity to any component of the study intervention (cyclophosphamide, mesna, fludarabine, IL-2). Or to the components of the TIL product including dimethyl sulfoxide (DMSO), human serum albumin, IL-2. Patients will be allowed if they have hypersensitivity to any of the supportive medications as long as there is acceptable alternative, per primary investigator.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

fludarabine; Cyclophosphamide

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Brian Orr, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

HCC Clinical Trials Office

CONTACT

843-792-9321; hcc-clinical-trials@musc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2032
• Last Updated: July 22, 2026

Record last verified: 2026-06

Locations

US (1)