Targeting HER2 in advanced solid tumors with modified CAR-T cells

Phase I/II Clinical Trial of HER2 Targeted HypoSti.CAR-T Cells in Treating Patients With HER2 Positive Local Advanced or Metastatic Solid Tumors

This study is testing a new type of CAR-T cell therapy to see if it can help people with advanced solid tumors that are HER2 positive and haven't responded to other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: prednisone, CAR-T, Chimeric antigen receptor
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05681650 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) designed to enhance the effectiveness of CAR-T cell therapy in treating HER2 positive advanced solid tumors. The study aims to assess the safety, feasibility, and efficacy of HypoSti.CAR-HER2 T cells in patients who have not responded to standard treatments. Participants will receive escalating doses of the modified CAR-T cells, with the trial structured in two phases: a dose escalation and a dose expansion phase. The approach is based on preclinical data demonstrating improved survival and expansion of CAR-T cells in hypoxic tumor environments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced or metastatic solid tumors expressing HER2 antigen and who have failed at least first-line treatment.

Not a fit: Patients with tumors that do not express HER2 or those who have not completed prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with HER2 positive advanced solid tumors that are resistant to current therapies.

How similar studies have performed: While CAR-T cell therapy has shown success in hematological malignancies, this approach in solid tumors is novel and has not been extensively tested in previous studies.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality

• Kaichao Feng — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Kaichao Feng, MD

Conditions HER2 Positive Advanced Solid Tumors