Evaluate the Safety, Tolerability, Dose-finding and Expansion of Intratumoral Injection of JCXH-211 Injection

• Status: Not yet recruiting
• Trial end date: 2025-08-24
• Target enrollment: 0
• Participant gender: All

Summary

This study is an open-label, dose-escalation and dose-expansion phase I clinical study. The study is divided into Phase 1a and Phase 1b.

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

Details

• Lead Sponsor: Immorna Biotherapeutics, Inc.

Criteria

Inclusion Criteria:

1. Male or female subjects, aged 18 to 75 years;

2. Subjects with malignant solid tumors confirmed by pathology and/or cytology who have progressed or are intolerant to standard treatment (except best supportive care). Including but not limited to head and neck cancer, liver cancer, melanoma, triple negative breast cancer, esophageal cancer, etc.

3. General condition score ECOG 0 ~ 1;

4. Expected survival of more than 3 months;

5. According to RECIST v1.1, the patient had at least one measurable tumor lesion with the longest diameter ≥10 mm at baseline (if lymph node, short diameter ≥15 mm).

6. There were lesions suitable for intratumoral injection (at least 10 mm in length and no more than 80mm in length) : a. For Part 1 of Phase Ia, the patient must have at least 1 skin/subcutaneous tumor lesion suitable for intratumoral injection. b. For Part 2 of Phase 1a: The patient must have at least 2 deep (visceral) lesions suitable for intratumoral injection; c. For Phase Ib (Part 3) : Patients must have at least one lesion suitable for intratumoral injection, which can be skin/subcutaneous tumor lesion or deep (visceral) lesion.

7. Part 1 patients in Phase Ia should present at least one tumor biopsy tissue before and after treatment;

8. Subjects should have sufficient bone marrow reserves or no hepatorenal coagulopathy, and laboratory values should be sufficient under the following conditions: a. Absolute neutrophil count > 1.5×10 9 /L and white blood cell count > 3×10 9 /L; b. Platelet count > 80×10 9 /L; c. Hemoglobin > 90g/L; d. Serum creatinine < 1.5× upper limit of normal (ULN) and creatinine clearance > 50 mL/min calculated by Cockroft-Gault formula; e. In the absence of confirmed liver metastasis, AST and ALT < 2.5×ULN; If there was confirmed liver metastasis, AST and ALT < 5×ULN; f. In the absence of liver metastasis, total bilirubin < 1.5×ULN; In patients with liver metastasis or Gilbert syndrome (hyperindirect bilirubinemia), total bilirubin < 3×ULN; g. International Standardized ratio (INR) < 1.5 and activated partial prothrombin time (APTT) < 1.5×ULN;

9. Patients without brain metastasis, or asymptomatic brain metastasis, or brain metastasis stable for more than 4 weeks after treatment;

10. At the start of study treatment, any previous systemic therapy must have been more than 4 weeks, and the toxicity of previous treatment must have recovered to grade 1 or less (except for patients with alopecia, vitiligo, peripheral neuropathy, or endocrine lesions treated by replacement therapy);

11. Female subjects must meet one of the following criteria: menopause for at least 12 consecutive months; surgery resulting in inability to have children; or use a reliable form of contraception. Appropriate contraception should be decided after discussion between the investigator and the subject. Female subjects of childbearing potential must agree to use reliable contraception during study treatment and for at least 180 days following the last dose of study drug. Females must have a negative pregnancy test within 72 hours prior to starting study drug;

12. Male subjects must agree to use contraception during study treatment and for at least 180 days after the last dose of study drug;

13. Subjects voluntarily signed the informed consent form.

Exclusion Criteria:

1. Known or suspected allergy to study drug ingredients or its analogues;

2. Patients who have previously received IL-12 therapy (alone or as part of a treatment regimen), except for patients who have participated in Part 1 of this study and are tolerant to a single intratumoral injection;

3. Patients who have previously received treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or have received treatment directed at another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137), and discontinued treatment due to Grade 3 or higher immune-related adverse events (irAEs);

4. Patients who have used immunosuppressive drugs within 2 weeks before the first dose, except intranasal, topical, inhaled corticosteroids, local steroid injection, systemic corticosteroids at physiological doses not exceeding 10 mg/day or equivalent or steroids as premedication for hypersensitivity;

5. Patients who were screened or scheduled to receive anticoagulant therapy during the study. Allow the use of low dose (preventive) anticoagulant drugs such as low molecular weight heparin, low dose farvaline, sulfonda liver decanosodium, etc.

6. Subjects with any other diseases or medical conditions that are unstable or may affect their safety or study compliance, any serious or uncontrolled systemic diseases, including severe heart disease (such as New York Heart Association Grade 3 or 4 congestive heart failure, acute coronary syndrome within 6 months), cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, severe infection, active gastrointestinal ulcers, abnormal immune function;

7. Uncontrollable ascites or pleural effusion;

8. Female subjects are pregnant or lactating;

9. Within 4 weeks before the first dose of study drug: a. received chemotherapy, radiotherapy, biological/targeted drug therapy, immune drug therapy, local therapy and other anti-tumor therapy; b. received major surgery; c. participated in other clinical trials, used or is using other experimental drug therapy (except non-interventional drug clinical trials);

10. Other severe, acute, or chronic diseases, clinical and laboratory abnormalities that may increase the risk of study and study drug, or may interfere with the study results;

11. Patients with active autoimmune disease or a history of autoimmune disease with a risk of recurrence, but patients with the following diseases are not excluded and can be further screened: A. type I diabetes mellitus; b. Hypothyroidism (if controlled with hormone replacement therapy alone); c. controlled celiac disease; d. Skin diseases that do not require systemic treatment (e.g. vitiligo, psoriasis, alopecia); e. Any other disease that will not recur in the absence of an external trigger;

12. Active human immunodeficiency virus (HIV), syphilis, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, asymptomatic chronic hepatitis B or hepatitis C carriers can be excluded; active HBV, HCV and HIV infection is defined as: a.HBsAg positive and HBV DNA ≥ 1000cps/mL (or 200 IU/mL); b. anti-HCV antibody and HCV RNA positive; c.HIV antibody positive;

13. Inability to tolerate intratumoral injection of JCXH-211 injection;

14. Patients with a history of organ or allogeneic bone marrow transplantation;

15. Subjects with intratumoral injection lesions located in the main airway, blood vessels or nerve bundles;

16. The investigator considers that the subject is not suitable for this trial for any reason.