Injection of immune cells to treat advanced solid tumors

An Open, Single-armed, Phase I Study to Evaluate the Safety and Efficacy Using Autologous TIL in Patients With Advanced Malignant Solid Tumors

This study is testing whether injections of immune cells can help people with advanced solid tumors, like melanoma and cervical cancer, feel better and fight their cancer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Juncell Therapeutics (industry)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT05417750 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial investigates the use of autologous tumor infiltrating lymphocytes (TIL) injections for patients with advanced malignant solid tumors. The study is divided into two parts: a dose escalation phase and an expanded enrollment phase, aiming to assess the safety and efficacy of TIL therapy. Participants will include those with various types of cancers, such as melanoma, cervical cancer, and non-small cell lung cancer. The trial is expected to enroll 20-60 participants over a period of 36 months.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced metastatic solid tumors and at least one measurable target lesion.

Not a fit: Patients with tumors that have not progressed after prior local therapies or those with an ECOG performance status greater than 1 may not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies utilizing TIL therapy have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Patients must be ≥18 and ≤75 years of age at the time of consent.
2. Patients with advanced metastatic solid tumors with clear pathological diagnosis, including melanoma, cervical cancer, head and neck squamous cell tumors, non-small cell lung cancer and breast cancer, etc.; while the expanded enrollment study plans to include those with melanoma, cervical cancer, and head and neck squamous cell tumors.
3. At least one measurable target lesion even after resection, as defined by RECIST1.1.

   Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatments was ≥3 months prior to Screening, and there has been demonstrated disease progression in that particular lesion.
4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Patients must have an estimated life expectancy of ≥3 months.
6. In the opinion of the Investigator, patients must be able to sign the ICF and complete all study-required procedures.
7. Patients must have the following hematologic parameters, Coagulation functions and hepatic and renal function:

   * White Blood Cell (WBC)≥2.5×10\^9/L；
   * Absolute Lymphocyte Count (ANC)≥1.5×10\^9/L;
   * Absolute Lymphocyte Count(ALC)≥0.7×10\^9/L;
   * Platelet≥100×10\^9/L；
   * International Normalized Ratio（INR）≤1.5×ULN;
   * Activated Partial Thromboplastin Time（APTT）≤1.5×ULN;
   * Serum Creatinine (Scr)≤1.5mg/dL (or 132.6μmol/L) or Creatinine Clearance≥60mL/min
   * Urinalysis: urine protein less than 2+, or 24-hour urine protein \<1g;
   * Alanine aminotransferase(AST/SGOT) ≤3×ULN;
   * Alanine aminotransferase (ALT/SGPT) ≤3×ULN;
   * Total Bilirubin(TBIL)≤1.5×ULN；
8. Patients must have a washout period ≥ 4 weeks from prior anticancer therapy(ies) to the start of the planned preconditioning regimen, including targeted therapy, chemotherapy, immunotherapy: anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)/anti-PD-1, other monoclonal antibody (mAb), or vaccine Palliative radiation therapy.
9. Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after receiving the last protocol-related therapy.
10. Patients must have no contraindications for surgery or biopsy.
11. Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period.

Exclusion Criteria:

1. Patients have not recovered from all prior therapy-related adverse events (AEs) to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0), except for alopecia or vitiligo, prior to Enrollment (tumor resection).
2. Patients who have received an organ allograft or prior cell transfer therapy.
3. Patients with symptomatic and/or untreated brain metastases (of any size and any number).
4. Patients who are on chronic systemic steroid therapy for any reason.
5. Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic ABX, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system.
6. Patients with systemic active infection requiring treatment, with positive blood culture or imaging evidence of infection, including active tuberculosis.
7. Patients with hepatic encephalopathy, hepatorenal syndrome, Child-Pugh class B or more severe cirrhosis, or liver failure.
8. Uncontrolled arterial hypertension（SBP≥160mmHg and/or DBP≥100mmHg）or any unstable cardiovascular or cerebrovascular disease in the recent 6 months of consent.
9. Patients who have a left ventricular ejection fraction (LVEF) \< 50% or New York Heart Association (NYHA) functional classification Class 3 or Class 4.
10. Female patients who are pregnant or breastfeeding.
11. Patients who are HIV positive, positive syphilis serological test, positive COVID-19 nucleic acid test, or clinically active hepatitis A, B, and C including virus carriers.

Where this trial is running

Beijing, Beijing

• Chinese PLA General Hospital — Beijing, Beijing, China (RECRUITING)

Study contacts

• Study coordinator: Mengmeng Tang

Conditions: Tumor Infiltrating Lymphocytes, Safety, Advanced Solid Tumor, Immunotherapy, Efficacy, Adverse Drug Event