Clinical trial NCT05417750: A Phase I Study on Autologous Tumor Infiltrating Lymphocytes Injection (GC101 TIL) for the Treatment of Advanced Malignant Solid Tumors
Official title: An Open, Single-armed, Phase I Study to Evaluate the Safety and Efficacy Using Autologous TIL in Patients With Advanced Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Tumor Infiltrating Lymphocytes
Safety
Advanced Solid Tumor
Immunotherapy
Efficacy
Adverse Drug Event
Lead sponsor: Shanghai Juncell Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-06-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 20-60 participants are expected to be enrolled for the Phase I clinical trial which is further divided into two parts: a "3+3" dose escalation study and an expanded enrollment study.

The Phase I clinical trial is expected to be finished in 36 months. To be specific, the dose escalation study plans to include patients with advanced malignant 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.


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.

Primary outcomes:
measure: Maximal Tolerance Dose
timeFrame: Up to Day 28
measure: Dose Limiting Toxicity
timeFrame: Up to Day 28
measure: Adverse Events
timeFrame: Maximum 360 days
Secondary outcomes:
measure: Disease Assessment for Duration of Response
timeFrame: Every 6 weeks for 12 months
measure: Disease Assessment for Disease Control Rate
timeFrame: Every 6 weeks for 12 months
measure: Disease Assessment for Progression-Free Survival
timeFrame: Every 6 weeks for 12 months
measure: Disease Assessment for Objective Response Rate
timeFrame: Every 6 weeks for 12 months
measure: Quality of Life Assessment
timeFrame: Every 6 weeks for 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
References: