Safety and Tolerability Evaluation of CEL001 Injection in Advanced Solid Tumors

A Phase I Clinical Study Evaluating the Safety and Tolerability of CEL001 Injection in the Treatment of Advanced Solid Tumors

This study is the first human, open label, dose escalation, and expansion phase I clinical trial aimed at evaluating the safety, tolerability, preliminary efficacy, pharmacokinetic characteristics, biomarker changes, and immunogenicity of CEL001 injection in the treatment of advanced solid tumors.

This study is divided into five stages: screening period, single dose period, clearing period, multiple dose period, and follow-up period. The observation period for single dose DLT is tentatively set at 14 days after administration, while the observation period for multiple dose DLT is tentatively set at 28 days after the first dose of multiple doses. The cumulative administration time from a single dose is tentatively set at no more than 1 year, and the follow-up period is tentatively set at 2 years after the last dose.

Inclusion Criteria:

• Subjects must meet all of the following criteria to enter this study:

  1. Age ≥ 18 years old, gender not limited;
  2. ECOG physical fitness status score: 0-1 points;
  3. Subjects with advanced or metastatic tumors diagnosed by histology or cytology, who have failed* or unable to tolerate standard treatment according to CSCO guidelines or NCCN guidelines, or lack effective treatment methods;
  4. Male subjects should weigh no less than 50 kilograms, and female subjects should weigh no less than 45 kilograms;
  5. Expected survival time exceeds 3 months;
  6. There must be at least one measurable lesion, defined as measurable according to the RECIST 1.1 standard;
  7. Prior to treatment, the main organ function meets the following criteria (no blood transfusion, long-acting EPO, or long-acting G-CSF treatment received within 14 days prior to the administration of the investigational drug, which can be reduced to 7 days for short acting EPO or G-CSF):

  1. Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelets ≥ 90 × 10^9/L, hemoglobin ≥ 90 g/L or ≥ 5.6 mmol/L;

  2. Kidney: serum creatinine ≤ 1.5 x upper limit of normal range (ULN) or Ccr ≥ 50 mL/min (estimated according to the Cockcroft Gault formula);

  3. Liver: Total bilirubin ≤ 1.5 × ULN (including liver metastasis or liver cancer subjects), AST and ALT ≤ 2.5 × ULN (including liver metastasis or liver cancer subjects ≤ 5 × ULN);

  4. Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN, Partially Activated Thromboplastin Time (APTT) ≤ 1.5 × ULN; 8. Women should agree to take appropriate contraceptive measures (such as intrauterine devices [IUDs], birth control pills, or condoms) during the study period and within 6 months after the end of the study. They must have a negative serum pregnancy test within 7 days prior to enrollment in the study and must be non lactating subjects; Men should agree to take appropriate contraceptive measures during the study period and within 6 months after the end of the study.

     • Standard treatment failure:

       • Non small cell lung cancer: (1) Subjects with metastatic non driver gene mutations: disease progression or recurrence after at least second-line treatment (including platinum based chemotherapy); (2) Subjects with driver gene mutations such as EGFR, ROS1, ALK in tumors should have received targeted therapy for these mutations that failed, followed by at least second-line treatment (including platinum based chemotherapy) for disease progression or recurrence;
       • Small cell lung cancer: disease progression or recurrence after receiving at least second-line treatment in the past;
       • Colorectal cancer: disease progression or recurrence after at least second-line treatment in the past (standard chemotherapy regimens include fluorouracil or its derivatives, oxaliplatin, and irinotecan, Subjects with BRAF V600E mutation have used BRAF inhibitors, and subjects with MSI-H/dMMR need to have used PD-1/PD-L1 treatment);
       • Head and neck squamous cell carcinoma: disease progression or recurrence after receiving at least second-line treatment (including platinum based chemotherapy) in the past;
       • Urethral epithelial cancer: disease progression or recurrence after receiving at least second-line treatment in the past (recommended treatment regimens in guidelines include PD-1/PD-L1 therapy, platinum based chemotherapy regimen, paclitaxel based chemotherapy regimen, vediximab, and vinblastine, and subjects with FGFR2/3 mutations have already used edatinib);
       • Esophageal cancer: disease progression or recurrence after receiving at least second-line treatment (including platinum based chemotherapy) in the past;
       • Cervical cancer: disease progression or recurrence after receiving at least second-line treatment in the past (including platinum based chemotherapy, subjects who meet PD-L1 positive or TMB-H or MSI-H/dMMR criteria must have received PD-1/PD-L1 treatment);
       • Hepatocellular carcinoma: disease progression or recurrence after receiving at least second-line treatment in the past;
       • Renal cell carcinoma: disease progression or recurrence after receiving at least second-line treatment in the past;
       • For other unspecified malignant tumors, refer to the latest guidelines of CSCO or NCCN.

Exclusion Criteria:

• Subjects who meet any of the following criteria will not be eligible to enter this study:

  1. Individuals allergic to any component of CEL001 injection, including those allergic to penicillin;
  2. Have received anti-tumor treatments such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or participated in other clinical trials within 4 weeks or 5 known drug half lives (whichever is shorter) before the first use of the investigational drug;
  3. Have received traditional Chinese medicine or modern Chinese medicine preparations with anti-tumor indications in the instructions within 14 days before the first administration;
  4. Within the past 5 years, have had malignant tumors other than those treated in this study (excluding cured thyroid cancer, basal cell carcinoma of the skin, and cervical carcinoma in situ);
  5. The adverse reactions of previous anti-tumor treatments have not yet recovered to NCI CTCAE v5.0 grade evaluation ≤ 1 (excluding toxicity judged by researchers to have no safety risks such as hair loss);
  6. Have undergone surgical procedures within 4 weeks prior to receiving treatment or have not fully recovered from any previous invasive procedures;
  7. If there are clinical symptoms of central nervous system metastasis or meningeal metastasis, or if there is other evidence indicating that the participant's central nervous system metastasis or meningeal metastasis has not been controlled, the researcher determines that it is not suitable for inclusion;
  8. Individuals with active infection (NCI CTCAE v5.0 ≥ 2) or any other suspected infection risk assessed by researchers;
  9. Have a history of autoimmune diseases, immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
  10. Subjects with active hepatitis B or active hepatitis C;
  11. Individuals who have previously received immunotherapy;
  12. Have a history of serious cardiovascular disease, such as severe cardiac rhythm or conduction abnormalities (requiring clinical intervention for ventricular arrhythmias, grade II-III atrioventricular block, etc.), myocardial infarction, history of coronary artery bypass surgery, heart failure, New York Heart Association (NYHA) classification of grade II or above, left ventricular ejection fraction (LVEF) ≤ 50% and thrombotic findings, male QTcF>450msec or female QTcF>470msec, etc; Subjects with a history of severe cerebrovascular disease such as stroke;
  13. It is necessary to combine other anti-tumor treatments (including various radiotherapy, chemotherapy, immunotherapy, targeted therapy, traditional Chinese medicine treatment, etc.);
  14. Have a clear history of neurological or mental disorders, including epilepsy or dementia;
  15. The researchers believe that there are other reasons why the subjects are not suitable to participate in this clinical study.