Safety and Efficacy of Intraperitoneal Injection of METR-NK Cells as Neoadjuvant Therapy for Advanced Epithelial Ovarian Cancer

Safety and Efficacy of Intraperitoneal Injection of METR-NK Cells as Neoadjuvant Therapy for Advanced Epithelial Ovarian Cancer: A Single-arm, Single-center, Exploratory Clinical Study

The goal of this type of clinical trial study is to evaluate the safety and efficacy of metabolic remodeling nature killer cells as neoadjuvant therapy in newly diagnosed patients with advanced ovarian cancer

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: METR-NK cell(Metabolic Remodeling Nature Killer Cells)

Detailed Description

Peripheral blood will be collected from a vein of arm. Peripheral blood mononuclear cells (PBMc) will be isolated and purified for NK manufacturing. The addition of key metabolic molecules in the medium remodeled the metabolic network of NK cells, significantly reduced the aging phenomenon of NK cells in the culture process, improved the cell activity of NK cells and enhanced the cytotoxicity of NK cells. After 14 days cultivation, activated METR-NK will be harvested and formulated for clinical administration.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bai-Rong Xia; Phone Number: 18604516165; Email: xiabairong9999@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Cancer Hospital
      • Contact: Bai-Rong Xia; Phone Number: 18604516165; Email: xiabairong9999@126.com
      • Contact: Yao Chen; Phone Number: 18379859820; Email: 1969354224@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 18-70 years old (≥18, ≤70);
• Open surgery, laparoscopic surgery, or coarse needle biopsy for histopathological confirmation of advanced (FIGO IIIC/IV stage) high-grade serous ovarian cancer, high-grade endometrioid carcinoma, primary peritoneal carcinoma, and/or fallopian tube carcinoma, etc.;
• ECOG score: 0-1;
• Blood and tissue specimens before, during, and after treatment can be obtained, and subjects agree to submit blood and tissue specimens to the central laboratory for the purpose of expanding research in this trial;
• At least one lesion measurable by CT/MRI according to RECIST 1.1 criteria;
• Expected survival of at least 3 months;

• Patients judged by professional gynecologic oncologists as unable to achieve R0 resection or intolerant to surgery.

  • Criteria for determining inability to achieve R0 resection include but are not limited to: Fagotti laparoscopic score ≥8 points; When laparoscopic evaluation is difficult to implement, an upper abdominal CT score ≥3 points may be used;
  • Criteria for intolerance to surgery may include: Advanced age: age ≥70; Body mass index: BMI ≥40.0; Multiple chronic diseases; Malnutrition or hypoalbuminemia; Moderate to large amount of ascites; Newly diagnosed venous thromboembolism (survival period greater than 12 weeks);
• Major organ function meets the following criteria within 7 days before treatment: Hematological examination: Hemoglobin ≥90g/L, white blood cell count ≥3×10^9/L, absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥90×10^9/L; Kidney: Serum creatinine <1.5 mg/dL, glomerular filtration rate (GFR) ≥50 ml/min (based on the Fairview Laboratories formula at screening); Liver: AST, ALT, and alkaline phosphatase <3 times the upper limit of normal for the institution, total bilirubin <1.5 times the upper limit of normal for the institution; Lung function: Resting oxygen saturation ≥90%; Cardiac function: Left ventricular ejection fraction (LVEF) ≥40% by echocardiography, MUGA, or cardiac MRI; no evidence of uncontrolled angina, severe uncontrolled ventricular arrhythmias, or acute ischemia or active conduction system abnormalities on electrocardiography;
• No history of intestinal obstruction within two months;
• Reproductive-age patients must take effective contraceptive measures;
• Subjects voluntarily join this study and sign an informed consent form (ICF);
• Good compliance is expected, and subjects are able to follow up on efficacy and adverse reactions as required by the protocol.

Exclusion Criteria:

• Patients who have received drugs or other cell immunotherapy in other clinical trials within 28 days before the screening period;
• Patients who have had other malignant tumors in the past 5 years;
• Acute illnesses are ongoing, or severe illnesses have occurred in the past 2 years, such as patients with active infections or fever, cardiovascular diseases (Grade III or IV heart failure), mental health issues (such as alcoholism, drug abuse);
• History of immunodeficiency, including HIV-positive status or other acquired, congenital immunodeficiency diseases;
• Organ transplant or organ failure patients, patients receiving immunosuppressive therapy after organ transplantation, or patients taking immunosuppressive drugs long-term;
• Thromboembolic events such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism within 6 months;
• Known allergy to any component of the final product of METR-NK preparation, including human serum albumin;
• Breastfeeding during the screening period or female subjects with positive serum or urine pregnancy tests;
• Patients with mental illnesses, including epilepsy, dementia, severe depression, bipolar disorder, etc.;
• Other conditions deemed unsuitable for inclusion by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: METR-NK cell（metabolic remodeling nature killer cells）; Intraperitoneal allogeneic METR-NK cells infusion ： Dilute 200 mL of METR-NK cells in 1500 mL of 0.9% saline solution at 37°C. The minimum amount of METR-NK cells infused each time should be no less than 7.5×10^7 cells per kilogram. Continuous infusion for 2 days constitutes one course, with 4 courses, with 13-day interval between each course

Drug: METR-NK cell(Metabolic Remodeling Nature Killer Cells); The minimum amount of METR-NK cells infused each time should be no less than 7.5×10^7 cells, Continuous infusion for 2 days constitutes one course, with 4 courses. The infusion is given every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	the percentage of patients received R0 resection after METR-NK cells as neoadjuvant therapy for advanced epithelial ovarian cancer	3-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete remission rate	No residual invasive carcinoma was found under the microscope, but ductal carcinoma in situ could be found; In addition, compare the amount of cancer cells in the specimen before and after the new adjuvant therapy, and use of the Miller Payne grading system to evaluate the effect of the new adjuvant therapy	3-month
Overall Response Rate (ORR) After Neoadjuvant treatment	Overall Response Rate according to RECIST1.1 after Neoadjuvant treatment. ORR is defined as the proportion of participants achieving Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST (v.1.1). Per RECIST 1.1, CR is defined as the disappearance of all target lesions; PR is defined as at least a 30% decrease in the sum of diameters of target lesions.	3-month
Disease control rate	the percentage of patients with complete response, partial response, and stable disease for more than 4 weeks in which response can be evaluated	3-month
Progression free survival	the date of enrollment to the date of the first onset of disease progression or death from any cause, whichever comes first	2-years
Survival rate	the date of enrollment to the date of death from any cause	3-years
Adverse event	Adverse medical events in clinical trial subjects treated with METR-NK cells	3-month

Collaborators and Investigators

• Sponsor: Anhui Provincial Cancer Hospital
• Collaborators: Anhui Kecheng intelligent health technology Co., LTD

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): May 2, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 2024 No. 050

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No