Targeting solid tumors with engineered CAR-T cells

Feasibility and Safety of Anti-PD-L1 Armored Anti-CD22 CAR-T/CAR-TILs Targeting Patients With Solid Tumors

This study is testing a new type of immune cell treatment for people with advanced solid tumors to see if it can better target cancer cells and cause fewer side effects than traditional therapies.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hebei Senlang Biotechnology Inc., Ltd. (industry)
• Drugs / interventions: CAR-T
• Locations: 1 site (Shijiazhuang, Hebei)
• Trial ID: NCT04556669 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of SL22P autologous CAR-T/CAR-TILs cells in patients with advanced malignant solid tumors. The study involves isolating T cells from either peripheral blood or tumor tissue, which are then modified to express an anti-CD22 CAR structure and an anti-PD-L1 scFv fragment. After transplantation back into patients, these engineered cells aim to target CD22+B cells and enhance anti-tumor immunity while potentially reducing adverse reactions compared to conventional treatments.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with advanced malignant solid tumors that have progressed despite standard treatments.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel and effective treatment option for patients with advanced solid tumors.

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

Eligibility criteria

Inclusion Criteria:

To be enrolled, subjects must meet all the following conditions:

1. Volunteer to participate in the clinical study, cooperate with the researcher to carry out the research, and sign the informed consent.
2. 18-75 years old (including boundary value), male or female;
3. Life expectancy ≥ 12 weeks;
4. Patients with ECOG score less than 2
5. All acute toxicity from prior antitumor therapy or surgery is reduced to level 0 to 2.
6. Patients with at least one measurable tumor focus according to recist1.1 standard;
7. Patients with advanced malignant solid tumors who still have disease progression under standard treatment, are intolerant to standard treatments, or lack effective standard treatments, and are pathologically confirmed;
8. Sufficient organ and bone marrow function, defined as follows:

   A) Neutrophil count (ANC) ≥ 1,500/mm3(1.5 × 109/L); B) Platelet count (PLT) ≥ 100,000/mm3 (100 × 109/L); C) Hemoglobin (Hb) ≥ 9 g/dL (90 g/L); D) Serum albumin ≥ 2.8g /dL; E) Serum creatinine ≤ 1.5 times the upper limit of normal value (ULN) or creatinine clearance rate ≥ 50 ml/min; F) Total bilirubin (BIL) ≤ 1.5×ULN, patients with liver metastasis or liver cancer ≤2×ULN; G) AST/SGOT or ALT/SGPT ≤ 2.5×ULN, patients with liver metastasis or liver cancer ≤ 5×ULN; H) International standardized ratio (INR) ≤ 1.5, prothrombin time (PT) and activated partial thrombin time (APTT) ≤ 1.5×ULN.
9. Patients with asymptomatic central nervous system (Central Nervous System, CNS) metastasis, or asymptomatic brain metastases after treatment, must be checked by computed tomography (CT) or magnetic resonance imaging (MRI) without disease progression, stable at least 3 Steroid medication is not required for at least 4 weeks..
10. Male patients and female patients of childbearing age should agree to take effective contraceptive measures from the signing of the informed consent form until 3 months after the last dose.

Exclusion Criteria:

1. Prior therapy with PD-L1 inhibitors
2. Prior therapy as follow:

   A) major surgery within 28 days prior to the first study drug treatment (biopsy required for diagnosis is permitted).

   B) Systemic therapy with immunosuppressive agents within 14 days before the first autologous of study drug, nasal spray and inhaled corticosteroids or physiological doses of steroid hormones are NOT excluded C) Vaccination with live attenuated vaccine within 28 days before the first study drug treatment or planned during the study period and 60 days after the end of the study drug treatment
3. With uncontrollable or symptomatic active central nervous system (CNS) metastasis. Patients with a history of CNS metastasis or spinal cord compression, but if the patient determined to have it stopped by using anticonvulsants and steroids before the first administration and could be clinically stable four weeks later, they may be enrolled in the study.
4. Patients with advanced symptoms, spread to the internal organs, or risk of life-threatening complications in a short-term (including patients with uncontrolled exudate \[chest, pericardium, abdominal cavity\]).
5. Have any active autoimmune disease or have a history of autoimmune disease and expected recurrence.

   Patients with skin diseases that require no systemic treatment, such as vitiligo, psoriasis, alopecia, type 1 diabetes, or childhood asthma that have been completely alleviated and may be included without any intervention as adults; Asthmatics required medical intervention with bronchodilators are excluded.
6. Had other active malignant tumors within 2 years before entering the study. Skin basal cell that can be treated topically and cured or squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary thyroid were excluded
7. Patients with seropositive response of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection;
8. Within 6 months before entering the study, the following conditions occurred: myocardial infarction, severe/unstable angina by New York Heart Association Patients with grade 2 or higher cardiac insufficiency and clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention.
9. Severe infection with no effective control.
10. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation is known.
11. Participated in any other drug clinical study within 4 weeks before the first administration, or no more than 5 half-lives before the last study.
12. A history of substance abuse or drug abuse is known.
13. The presence of other serious physical or mental illness or laboratory test abnormalities that may increase the risk of participating in the study or interfere with the results of the study, as well as patients whom the investigator deems inappropriate for participating in the study.

Note: Severe infection refers to sepsis or uncontrolled infection, which can be included in the group only after infection.

Exit criteria :

Withdrawal: This can be divided into investigator performed withdrawal and patient 's voluntary withdrawal from the clinical trial

1. Withdrawal implemented by the investigator: When the patients meets the suspension criteria specified in the protocol during the trial, such as: vital organ dysfunction, drug allergic reaction, poor compliance, worsening of the disease, or serious adverse reactions, it is necessary to stop the trial drug treatment or adopt other treatment methods During treatment, the researcher asked the patients to withdraw from the trial. Due to the differences of patients ' cells, there was a possibility that insufficient number of CAR-T cell can't be prepared.Thus, the investigator judges that the patient needs to withdraw from the study.
2. Patient's withdrawal: such as poor efficacy, intolerance of adverse reactions, hope to adopt other treatment methods, or voluntarily withdraw from the trial without any reason

Where this trial is running

Shijiazhuang, Hebei

• Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (RECRUITING)

Study contacts

• Principal investigator: Zhiyu Wang — Hebei Medical University Fourth Hospital
• Study coordinator: Zhimeng Qiu

Conditions: Solid Tumor, Adult, Cervical Cancer, Sarcoma, NSCLC, CD22, chimeric antigen receptor, solid tumor, tumor infiltration lymphocyte