Phase I Study of SGN1 in Patients With Advanced Solid Tumor

• Status: Not yet recruiting
• Trial end date: 2024-01-31
• Target enrollment: 0
• Participant gender: All

Summary

Objectives:To assess the safety and tolerability followed by a dose expansion study to characterize safety, and preliminary efficacy of SGN1,a genetically modified strain of Salmonella enterica, serotype typhimurium (VNP20009-M) that expresses L-Methioninase,in participants with refractory 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:The treatment populations shall be patients presenting with histologically confirmed advanced and/or metastatic solid tumors that are refractory to standard curative therapy and for which no other conventional therapy exists.

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

Details

• Lead Sponsor: Guangzhou Sinogen Pharmaceutical Co., Ltd

Criteria

Inclusion Criteria:

• Participants must meet all the following inclusion criteria:

1. Age 18-75 years inclusive of end value, regardless of gender

2. Part 1: Patients with advanced stage (unresectable or metastatic) cancer primarily including non-small cell carcinoma (adeno- and squamous), sarcoma, cervical carcinoma, and hepatocellular carcinoma characterized by failure of any standard treatment (disease progression or intolerance, such as chemotherapy, targeted therapy, and other immunotherapies) or subjects who have no standard treatment or subjects who are unable to receive standard treatment. Part 3: Patients who meet all the standards above and should be the selected tumor type according to part1&2.

3. Patients finished anti-tumor therapy including chemotherapy, immunotherapy, biological agents, hormone therapy, radiotherapy (except local radiotherapy for pain relief) ≥ 4 weeks prior to the first dose of study drug.

4. At least 1 measurable lesion according to RECIST 1.1

5. Patients have recovered from any toxic reaction to previous medications (≤Grade 1 based on NCI-CTCAE v 5.0, except hair loss)

6. Eastern Co-Operative Oncology Group (ECOG) performance status 0 ~ 1 and a life expectancy of at least 3 months.

7. Laboratory tests must meet the following requirements and have not received any blood cell growth factor 14 days before the test (Participants with laboratory values outside of the specified ranges will be permitted to be retested once in order to meet the criteria):

1. absolute count of neutrophils (ANC) ≥1.5×109/L, platelet ≥75×109/L; Hemoglobin ≥90 g/L;

2. serum albumin ≥ 25g/L; Bilirubin ≤1.5×ULN, ALT and AST ≤2.5 × ULN;

3. In patients with liver metastasis, ALT and AST≤5×ULN;

4. Creatinine clearance ≥50 mL/min (standard Cockcroft -Gault formula) or Cr ≤1.5 ×ULN:urinary protein ≤2+ or urinary protein quantitative <1.0g/L.

8. 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.

9. 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.

10. 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.

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

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

Exclusion Criteria:

• Patients will be excluded from participation for any of the following criteria:

1. Received systemic or absorbable dosage of steroid hormone (prednisone, dexamethasone or equivalent) of >10 mg/day in the 14 days prior to enrollment;

1. Prednisone >10 mg/day

2. Dexamethasone >1.5 mg/day

2. Present with symptomatic central nervous system metastasis or brain abscess at screening;

3. Present with diverticulitis or conditions at screening that might promote the unintentional growth of anaerobic bacteria in nontarget lesions;

4. Existing cardiac clinical symptoms or diseases that cannot be well controlled, such as:

1. NYHA grade 2 or above heart failure;

2. Unstable angina pectoris;

3. Myocardial infarction occurred within 1 year;

4. Patients with supraventricular or ventricular arrhythmias that have clinical significance and need treatment or intervention; or

5. Uncontrolled hypertension (systolic blood pressure) ≥160 mmHg and (diastolic blood pressure) ≥100 mmHg after drug treatment;

5. Those who had received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy that ended fewer than 4 weeks before the first dose of study treatment (if nitrosourea or mitomycin chemotherapy the interval between end of chemotherapy and first dose of study treatment must be no less than 6 weeks);

6. Patients with active or uncontrolled infection or fever, >38.5℃, of unknown cause during screening or before the first administration of the study drug (according to the judgment of the researcher, fever caused by tumor can be included);

7. 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;

8. Received live or attenuated vaccines within 4 weeks of study drug administration, during treatment, or within 5 months of the last administration;

9. 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;

10. In the researcher's judgment, patients who are not suitable for other reasons;

11. Documented salmonella infections within 6 months;

12. Currently using antibiotic.

13. Allergic to any study medications or rescue medications

14. Subjects with implants such as pacemakers, prosthetic cardiac valves, or metal orthopedic prostheses.