A Clinical Study of Anti-CD70 UCAR-T in Relapsed or Refractory Solid Tumors

NCT06383507 | Not Yet Recruiting Phase 1

• 1 other identifier: CHT101
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, single-arm ，open-label ，dose escalation and dose extension study. In this study we plan to evaluate the safety and efficacy of CD70-targeting UCAR-T cells in the treatment of CD70-positive refractory or relapsed solid tumors, and obtain recommended doses and infusion patterns.

Conditions

Metastatic Tumor; Advanced Solid Tumor; Renal Cell Carcinoma; Ovarian Cancer; Cervix Cancer; Head and Neck Squamous Cell Carcinoma; Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse events after CD70 UCAR-T cells infusion (Safety and Tolerability)

  Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

  28 days

Secondary Outcomes (2)

• Disease control rate (DCR)

  42 days

• Objective response rate (ORR)

  42 days

Study Arms (1)

Anti-CD70 UCAR-T Cell Injection

EXPERIMENTAL

In the discovery phase, accelerated titration combined with the "3+3" dose escalation principle was adopted, starting from the initial dose of 3×106/kg. If a grade ≥3 AE occurs during DLT observation, the accelerated titration mode will switch to "3+3" dose escalation, at least 12 eligible patients will be enrolled and receive 4 doses of CD70 UCAR-T cell therapy (3 × 10\^6 cells/kg, 6 × 10\^6 cells/kg, 8× 10\^6 cells/kg, 1 × 10\^7 cells/kg). In the dose expansion phase, each group will choose one or two dose groups to verify the safety and efficacy, and plan to recruit about 6 subjects in each dose group.

Drug: CHT101

Interventions

CHT101 DRUG

After lymphodepletion with Fludarabine and Cyclophosphamide, CD70 UCAR T cells were transfused intravenously.

Anti-CD70 UCAR-T Cell Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and sign a written informed consent documen；
• Age ≥18 years old, male or female；
• Histopathological confirmed advanced or metastatic solid tumors failed to at least second-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy；
• Histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) diagnosed as advanced/metastatic solid tumor (positive tumor CD70 expression (tumor CD70 positive (IHC 2+) confirmed by histology or pathology));
• At least one measurable lesion at baseline per RECIST version 1.1；
• The expected survival time is more than 12 weeks;
• ECOG 0-1 points;
• The function of important organs is basically normal:Hematopoietic function:
• Hematopoietic function: neutrophils ≥ 1.5×109/L, platelets ≥ 90×109/L, hemoglobin ≥ 90g/dL;
• Renal function: serum creatinine≤1.5×ULN;
• WBC≥3.0×109/L,
• Liver function: Total bilirubin ≤ 1.5×ULN(Except Gilbert syndrome), extrahepatic metastasis：ALT and AST ≤ 3.0×ULN (Nonhepatic metastasis：it can be relaxed to ≤ 5.0×ULN);
• coagulation function：INR≤1.5×ULN，APTT≤1.5×ULN
• Subjects agree to use reliable and effective contraceptive methods for contraception within 6 months after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);

You may not qualify if:

• Received anti-CD70 drug treatment before screening;
• Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is longer) before Received;
• Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to Received；
• Pregnant, lactating, or breastfeeding females;
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV) RNA titer test is greater than the normal range; human immunodeficiency virus (HIV) antibody positive; syphilis test positive; cytomegalovirus (CMV) DNA test positive;
• Have any of the following heart conditions:
• New York Heart Association (NYHA) stage III or IV congestive heart failure; Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment; Clinically significant ventricular arrhythmia, echocardiography showed cardiac ejection fraction\<50%,
• Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;
• Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation;
• Vaccination within 14 days of study enrollment;
• Received live attenuated vaccine within 4 weeks before screening;
• Malignant tumors other than the target tumor within 3 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 3 years prior to enrollment;
• Other investigators deem it inappropriate to participate in the study.
• Serious or uncontrollable systemic disease or any unstable systemic disease, including but not limited to uncontrolled hypertension, uncontrolled hyperglycemia, liver and kidney insufficiency or metabolic disease, central nervous system disease, etc

Sponsors & Collaborators

• Zhejiang University: lead

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Renal Cell; Ovarian Neoplasms; Uterine Cervical Neoplasms; Squamous Cell Carcinoma of Head and Neck; Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Central Study Contacts

Weijia Fang, MD

CONTACT

691655; weijiafang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: April 22, 2024
• Primary Completion (Estimated): April 21, 2027
• Study Completion (Estimated): April 21, 2029
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share