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Clinical Trials in China / NCT05681650
Recruiting Phase 1/2

HER2 Targeted HypoSti.CAR-T Cells in HER2 Positive Advanced Solid Tumors

NCT05681650 · tracked via the Priya Life Science China tracker
Sponsor
Chinese PLA General Hospital
Phase
Phase 1/2
Started
2023-10-11
Last updated
2023-12-12

Condition(s) studied

HER2 Positive Advanced Solid Tumors

Investigational drug(s) / intervention(s)

HypoSti.CAR-HER2 T cellsAlbumin-bound paclitaxel →Cyclophosphamide →Fludarabine →

HypoSti.CAR-HER2 T cells: Dose escalation: dose -1 (1×10\^6 cells/kg) ,dose 1 (3×10\^6 cells/kg) , dose 2 (6×10\^6 cells/kg), dose 3 (1×10\^7 cells/kg), dose 4 (1.5×10\^7 cells/kg). Dose expansion: RP2D

Albumin-bound paclitaxel: Administered intravenously at dose of 100-200mg/m2 on day -5

Cyclophosphamide: Administered intravenously at a total dose of 15-30mg/kg on day -3 and day-2

Fludarabine: Administered intravenously at dose of 30mg/m2/d on day -3 and day -2 only in the first infusion of HypoSti.CAR-HER2 T cells

Study summary

Chimeric antigen receptor modified T (CAR-T) cell therapy still has multiple difficulties in solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity. In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment. After accomplishment of animal model verification, investigators conduct this clinical trial in order to assess the in vivo safety, feasibility and efficacy of HypoSti.CAR-HER2 T cells in HER2 antigen positive advanced solid tumors.

Eligibility

Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria: * 1\. Age from 18 to 75 years with estimated life expectancy \>3 months. * 2\. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. HER2 antigen expression percentage ≥ 30%. * 3\. Have at least one measurable target lesion. * 4\. Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study. * 5\. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to \<= grade 1 toxicity. * 6\. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment. * 7\. Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs. * 8\. Previous treatment with anti-PD-1/PD-L1 antibodies are allowed. * 9\. Ability to understand and sign a written informed consent document. * 10\. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug. Exclusion Criteria: * 1\. Active, known or suspected autoimmune diseases. * 2\. Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening. * 3\. Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. * 4\. History of severe hypersensitive reactions to other monoclonal antibodies. * 5\. History of allergy or intolerance to study drug components. * 6\. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. * 7\. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function. * 8\. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient. * 9\. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). * 10\. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented. * 11\. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\]. * 12\. Vaccination within 30 days of study enrollment. * 13\. Active bleeding or known hemorrhagic tendency. * 14\. Subjects with unhealed surgical wounds for more than 30 days. * 15\. Being participating any other trials or withdraw within 4 weeks.

Primary outcome measure(s)

Trial sites (1)

FacilityCityRegionStatus
Kaichao Feng Beijing Beijing Municipality Recruiting

More Chinese PLA General Hospital trials in China

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05681650 on ClinicalTrials.gov ↗ ← All trials in China