CD40 Ligand Expressing MSLN-CAR T Cell Therapy in MSLN Positive Advanced/Metastatic Solid Tumors

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

In preclinical study, investigators have demonstrated that the newly developed CD40 ligand expressing MSLN-CAR T cells possess more powerful antitumor activity than previously reported CAR-MSLN T cells in animal models. In this clinical trial, at least 9 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD40 ligand expressing MSLN-CAR cell therapy according to the "3+3" principle. In dose expansion period, additional 10 to 21 patients will be enrolled to receive CD40 ligand expressing MSLN-CAR T cell therapy at dose of RP2D.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chinese PLA General Hospital
• Collaborator: UTC Therapeutics Inc.
• Treatments: Albumin-Bound Paclitaxel; Cyclophosphamide; Paclitaxel

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. Mesothelin antigen expression percentage ≥ 10%.

• 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.