Study of SGN1 Administered Via Intratumoral Injection in Patients With Advanced Solid Tumor

• Status: Not yet recruiting
• Trial end date: 2025-04-04
• Target enrollment: 0
• Participant gender: All

Summary

Objectives：To characterize safety, tolerability, MTD and RP2D, PK, biological distribution, immunogenicity, and preliminary efficacy of intratumoral injection of SGN1 in patients with advanced solid tumors.

Study Rationale:The mechanism of action for SGN1 is based on the fact that most tumors are methionine dependent. SGN1 is designed to be used as a tumor therapeutic bacterium that can preferentially replicate and accumulate in tumors and starve them of essential amino acids by delivering the oncolytic enzyme L-Methioninase.

Patient Population:Patients with advanced head and neck squamous cell carcinoma(HNSCC), who have disease progression after receiving at least one standard systemic treatment in the past, or who are intolerant to or unable to receive the curative or life-prolonging standard of care available therapies. Patients should have target lesions suitable for intratumoral injection of SGN1.

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

Details

• Lead Sponsor: Guangzhou Sinogen Pharmaceutical Co., Ltd

Criteria

Inclusion Criteria:

1. Male of females aged 18~75 years.

2. Parts 1 and Part 2: Patients with histologically or cytologically proven advanced solid tumors, including but not limited to the following tumor types: head and neck tumor, penis carcinoma, lung cancer, lymph node metastasis of skin cancer, Hodgkin's lymphoma or non-Hodgkin's lymphoma, osteosarcoma, etc., who are not eligible or are unable to receive curative or life-prolonging standard of care available therapies; patients must have the main target lesions suitable for the local injection of SGN1;

3. Part 3: the specific tumor-type expansion study may enroll the following patients: • Patients with HNSCC who have failed to standard therapy or who are intolerant to the standard treatment;

4. Patients must have the main target lesions suitable for the local injection of SGN1. The tumors must be in situ or metastatic solid tumors that are subcutaneous, palpable, or can be injected directly under image guidance and by an interventional radiologist or specialist with adequate qualifications and trainings, provided that these tumors do not invade the walls of blood vessels or hollow organs confirmed by the previous imaging studies.

5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0- 1;

6. Life expectancy ≥ 12 weeks;

7. Patients who have recovered from any toxic reaction to previous medications (≤Grade 1 based on NCI-CTCAE v 5.0) (except other toxicities such as hair loss that will not present the safety risk for patients as evaluated by the investigators);

8. At least one measurable lesion as determined by RECIST 1.1;

9. Adequate organ and bone marrow functions defined as follows (except for the use of any blood cell growth factors during the screening period):

Hematological

• Absolute Neutrophil Count (ANC) ≥ 1.5 ×109 /L

• Blood Platelet Count (BPC) ≥ 90 ×109 /L

• Hemoglobin ≥ 9.0 g/dL (No blood transfusions within 14 days prior to screening) Hepatic

• Total bilirubin (BIL) ≤ 1.5 × upper limit of normal (ULN)( BIL≤ 2×ULN is allowed when there is liver metastasis)

• AST and ALT ≤ 2.5 × ULN (AST, ALT ≤ 5 × ULN is allowed when there is liver metastasis) Renal

• Serum albumin ≥ 2.8 g/dL

• Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥50 ml/min; - Urine protein <2+, or quantitative urine protein<1.0g/L Coagulation

• International normalized ratio (INR) ≤1.5×ULN,

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5×ULN.

10. If female, be either postmenopausal for at least 1 year with documented follicle stimulating hormone (FSH) >30 IU/L, or surgically sterile for at least 3 months, or if a woman of childbearing potential, must be non-pregnant confirmed by blood and urine pregnancy tests, and non-lactating.

11. If sexually active; women must practice a medically effective double barrier birth control (such as a condom with spermicide) during the study and for at least 5 months after the last dose; or other effective method during the study (e.g. oral, injectable or implanted contraceptive medications or intrauterine devices), Abstinence may be considered an acceptable method of contraception at the discretion of the investigator, but the participant must agree to use one of the acceptable birth control methods if she becomes sexually active

12. If sexually active; men must use a medically effective barrier of safety (such as a condom) or practice abstinence; men with a female partner of child bearing potential must practice abstinence or use a physician approved manner of contraception for at least 5, months after the last dose

13. Patients must be able to follow up after the treatment

14. Patients must understand and voluntarily sign the informed consent form.

Exclusion Criteria:

1. Prior treatment with oncolytic bacteria;

2. Patients with extremely large tumor (the longest diameter of a single tumor exceeds 8 cm);

3. Patients who are known to be allergic to the investigational drug or any of its excipients; or have a severe allergic reaction to other monoclonal antibodies;

4. Patients who have received the following treatments or drugs before the first treatment with the investigational drug:

1. Major surgery performed within 28 days before the first treatment with the investigational drug (biopsy is allowed for diagnostic purposes);

2. Immunosuppressive drugs have been administered within 14 days before the first treatment with the investigational drug, excluding corticosteroid nasal sprays and inhaled corticosteroids or physiological doses of systemic steroid hormones (i.e. prednisone not exceeding 10 mg/d or equivalent physiological doses of other corticosteroids);

3. Inoculation of (attenuated) live virus vaccine: within 28 days before the first dosing of study drug, or during the study period or 60 days after the last dose of study drug;

4. Any anti-tumor therapies (including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biological therapy or tumor embolization) within 28 days before the first dosing of the investigational drug(if nitrosourea or mitomycin chemotherapy the interval between end of chemotherapy and first dose of study treatment must be no less than 6 weeks);

5. Patient with known uncontrollable or symptomatic active CNS metastases, manifested by clinical symptoms, brain edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth. Patients with a history of metastases to the central nervous system or spinal cord compression can be included in the study if they have clearly received treatment and have shown stable clinical manifestations after the discontinuation of anticonvulsants and steroids for 4 weeks before the first dose of the investigational drug;

6. Symptomatic, advanced patients whose tumors have spread to the internal organs and are at risk of life-threatening complications in the short term (including patients with uncontrollable large amounts of effusion (thoracic cavity, pericardial cavity, or abdominal cavity);

7. Patients with any active autoimmune diseases or a history of any autoimmune disease with predictable recurrence (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [only subjects whose condition can be controlled by hormone replacement therapy can be included]; Subjects with skin diseases that do not require systemic treatment such as vitiligo, psoriasis, hair loss, Type I diabetes mellitus, or those with childhood asthma which has been completely relieved and requires no interventions in adulthood, can be included. Those with asthma who need bronchodilators for medical intervention cannot be included);

8. Patients with other active malignant tumor(s) within 2 years before entering the study. Subjects with history of cervical carcinoma in situ, superficial or non-invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent may be included at the judgment of the Investigator;

9. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as: hepatitis B virus surface antigen [HBsAg] testing positive, HBV DNA ≥ 500 IU/ml and abnormal liver function; hepatitis C, defined as: hepatitis C antibody [HCV-Ab] testing positive, higher HCV-RNA than the lower limit of detection of the analysis method and abnormal liver function) or hepatitis B and hepatitis C co-infection;

10. Within 6 months before entering the study, patients received clinical intervention due to the following conditions: myocardial infarct, severe/unstable angina pectoris, NYHA grade II-IV cardiac insufficiency, and clinically significant supraventricular or ventricular arrhythmia;

11. Systemic use of antibiotics for ≥7 days within 4 weeks before the first administration, or fever > 38.5°C of unknown cause or before the first administration of the study drug (according to the judgment of the researcher, fever caused by tumor can be included);

12. Patients who have concomitant infectious diseases and require concomitant medications;

13. Diverticulitis that may cause anaerobic bacteria to multiply;

14. Documented salmonella infection within 6 months;

15. Known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant;

16. Patients participating in other clinical studies or participating in other clinical studies within 4 weeks (or 5 half-lives of other study drugs) prior to enrollment and receiving experimental drug administration;

17. Known history of psychotropic drug abuse or recreational drug abuse;

18. In the judgment of the investigator, there are other factors that may lead to termination: for example, other serious diseases (including mental diseases) need to be treated together, there are serious abnormalities in laboratory examination, family or social factors, which may affect the safety of the participants or test data and sample collection.