CD70-targeted CAR-T treatment for advanced gynecologic cancer

A Phase I Clinical Study to Assess the Safety and Efficacy of CD70-targeted CAR-T in the Treatment of CD70-positive Advanced/Metastatic Gynecologic Cancer

This study is testing a new CAR-T treatment that targets CD70 to see if it can help people with advanced gynecologic cancers feel better and improve their outcomes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: CAR T, chemotherapy, radiation, prednisone, CAR-T
• Locations: 1 site (Wuhu, Anhui)
• Trial ID: NCT06215950 on ClinicalTrials.gov

What this trial studies

This clinical research evaluates the safety and efficacy of CD70-targeting CAR-T cells in patients with CD70-positive advanced or metastatic gynecologic cancers. The study is designed as a single-center, double-arm, open-label trial, consisting of a dose discovery phase and a dose expansion phase. Participants will be assigned to either an intravenous infusion group or an intraperitoneal injection group, with a total of approximately 18 subjects recruited across different dose levels. The aim is to determine recommended doses and infusion patterns while assessing the treatment's safety and effectiveness.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with CD70-positive advanced or metastatic gynecologic tumors who have failed or are intolerant to standard treatments.

Not a fit: Patients with non-CD70-positive tumors or those who have not progressed after standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with advanced gynecologic cancers that express CD70.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this specific approach targeting CD70 in gynecologic cancers is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years old;
2. Advanced/metastatic gynecological tumor confirmed by histopathology or cytology (paraffin sections or fresh biopsy tumor tissue specimens) (CD70 positive tumor expression (CD70 positive tumor confirmed by histology or pathology (IHC 3+));
3. Failure or intolerance after standard treatment (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), and currently no effective treatment;
4. According to the RECIST version 1.1 standard, there is at least one measurable diameter and evaluable target lesion. Measurable lesions are defined as: extranodal lesions with CT scan diameter ≥10mm, lymph node lesions with CT scan diameter ≥15mm, scan layer thickness ≤ 5mm, and have not received local treatment;
5. ECOG 0 \~ 2 points ;
6. Expected survival time is more than 12 weeks;
7. No serious mental disorders;
8. The functions of important organs are basically normal:

   1. Hematopoietic function: neutral granules \>1.0×109/L, platelet \>75×109/L, hemoglobin \>80g/L;
   2. Cardiac function: Echocardiography indicated cardiac ejection fraction ≥50%, and no obvious abnormality was found in electrocardiogram;
   3. Renal function: serum creatinine ≤2.0×ULN;
   4. Liver function: ALT and AST ≤2.0×ULN (patients with liver tumor infiltration can be relaxed to ≤3.0×ULN);
   5. Total bilirubin ≤2.0×ULN (Gilbert syndrome or liver tumor infiltration can be relaxed to ≤3.0×ULN);
   6. Blood oxygen saturation in non-oxygen state\>92%.
9. Have the criteria for simple or intravenous blood collection, and no other contraindications for cell collection;
10. The subject agrees to use a reliable and effective contraceptive method for contraception (excluding safe period contraception) within 1 year from signing the informed consent to receiving the CAR T cell infusion;
11. The subject or his/her guardian agrees to participate in the clinical trial and signs the ICF, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

Exclusion Criteria:

1. Received anti-CD70 drug therapy before screening;
2. Active/symptomatic central nervous system metastasis or meningeal metastasis at the time of screening; Treated subjects with brain metastases can only be enrolled if no radiographically demonstrated progression is demonstrated ≥4 weeks after the end of treatment.
3. Received any of the following treatments prior to screening:

   1. Participated in other interventional clinical studies before screening, including: the time of last use of unmarketed new drugs less than 3 months from cell transfusion, or the time of last use of marketed drugs less than 5 half-lives from cell transfusion;
   2. Received anti-tumor therapy such as chemotherapy or targeted therapy within 2 weeks of preapheresis or at least 5 half-lives (whichever is shorter); Received systemic radiation within 4 weeks and local radiation within 2 weeks; Or received radioactive drugs (strontium, samarium) within 8 weeks prior to treatment.
   3. Systemic corticosteroid therapy with doses greater than 10mg/ day of prednisone (or equivalent doses of other corticosteroids) within 2 weeks of preapheresis (in the absence of active autoimmune disease, inhaled or topical steroid use and adrenocortical replacement with doses greater than 10mg/ day of prednisone efficacy dose are permitted);
   4. Received live attenuated vaccine within 4 weeks prior to screening;
4. There is an active or uncontrolled infection requiring systemic treatment within 1 week prior to screening;
5. Had malignancies other than the target tumor within 3 years prior to screening, except for malignancies that had received radical treatment and had no known active disease for ≥3 years prior to enrollment; Or adequately treated non-melanoma skin cancer with no evidence of disease;
6. Have any of the following heart conditions:

   1. New York Heart Association (NYHA) Stage III or IV congestive heart failure;
   2. Had myocardial infarction or coronary artery bypass grafting (CABG) within ≤6 months before enrollment;
   3. A history of clinically significant ventricular arrhythmia, or unexplained syncope (other than those caused by vasovagal or dehydration);
   4. History of severe non-ischemic cardiomyopathy.
7. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.
8. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal range; Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal range; Positive for human immunodeficiency virus (HIV) antibodies; Syphilis positive; Cytomegalovirus (CMV) DNA test positive;
9. The subject has a history of venous embolism (e.g., pulmonary embolism) and currently requires anticoagulant therapy, or if: a. Bleeding with grade 3 to 4 persists for more than 30 days; b. have sequelae from venous embolism (e.g. persistent dyspnea and hypoxia); (Note: Participants who have venous embolism but do not meet the above criteria can participate in the test);
10. Poorly controlled hypertension, defined as systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥90mmHg (Blood pressure values are measured based on the average of 3 readings at least 2 minutes apart, patients with blood pressure ≥150/90 MMHG at initial screening may receive antihypertensive treatment, if well controlled after treatment, And blood pressure \< 150/90mmHg can be screened);
11. Women who are pregnant or breastfeeding, and male or female subjects who plan to have a family within 1 year after receiving CAR T cell transfusion;
12. Conditions deemed unsuitable for participation in the study by other researchers.

Where this trial is running

Wuhu, Anhui

• The First Affiliated Hospital of Wannan Medical College — Wuhu, Anhui, China (Recruiting)

Study contacts

• Principal investigator: Guantai Ni, M.D — First Affiliated Hospital of Wannan Medical College
• Study coordinator: Guantai Ni, M.D

Conditions Ovarian Cancer; Cervix Cancer; Metastatic Cancer; Advanced Cancer; Gynecologic Cancer; CAR-T; CD70