Summary

Eligibility
for people ages 18-75 (full criteria)
Location
at Orange, California and other locations
Dates
study started
estimated completion

Description

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 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 therapy and for which no other conventional therapy exists.

Official Title

Phase I, Open-label Study to Evaluate Safety, Tolerability and Preliminary Efficacy of Modified Salmonella Typhimurium SGN1 in Patients With Advanced Solid Tumor

Details

Methionine starvation can powerfully modulate DNA methylation, cell cycle transition, polyamines and antioxidant synthesis of tumor cells, in contrast to normal ones. L-Methioninase is a pyridoxal phosphate dependent enzyme that catalyzes the γ-elimination reaction of L-methionine to methanethiol, α-ketobutyrate and ammonia. Absolute-dependency on exogenous supply of L-methionine, not homocysteine, for growth and proliferation of tumors is the pivotal biochemical criterion for various human cancers. SGN1 is a genetically modified strain of Salmonella enterica, serotype typhimurium that expresses L-Methioninase. The attenuated live bacterium has been investigated in China for utility in treating advanced solid tumors. 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. This study is a multi-center phase I clinical trial with 3 parts: Part 1 & 2 is an open-label, dose escalation phase. Part 1 is the DLT observation period, and the patients will enter part 2 for extension treatment after completing the 28-day DLT observation period. In part 1& 2 of the study will employ a standard 3 + 3 escalating dose design to explore dose limiting toxicities (DLTs) in sequential cohorts to select the maximum tolerated dose (MTD). In part 2, the treatment may be terminated if the patients withdraws, has unacceptable toxicity, develops disease progression, experiences an AE that cannot be resolved with/without rescue medication in 2 weeks (14 days), death, or loss to follow-up. In such cases, patients will be discontinued and palliative or rescue therapy will be offered to those that terminate early. Part 3 is an open-label study designed to adopt the optimal biologic dose in no more than 2 specific tumor subtypes. The tumor types will be selected based on safety and preliminary efficacy evaluated in Part 1&2. A preliminary determination of optimal biologic dose shall be defined as the lowest dose that has the highest efficacy rate (i.e., the dose at the beginning of the plateau of the dose-efficacy curve). The dose expansion study will be 10 patients per specific tumor subtype, who may be treated until the patients withdraws, has unacceptable toxicity,has disease progression, has AE that cannot be resolved with/without rescue medication in 2 weeks (14 days),death,or loss to follow-up. SGN1 will be administrated weekly and Tumor assessments are performed every 6 weeks post first dose.

Keywords

Advanced Solid Tumor, Neoplasms, SGN1

Eligibility

You can join if…

Open to people ages 18-75

  • Participants must meet all the following inclusion criteria:
  • Age 18-75 years inclusive of end value, regardless of gender.
  • Part 1: Patients with advanced stage (unresectable or metastatic) cancer including but not limited to small cell lung cancer, non-small cell lung cancer (adeno- and squamous), Hodgkin's lymphoma or non-Hodgkin's lymphoma, sarcoma, cervical carcinoma, melanoma, head and neck cancer, breast cancer, ovarian cancer, pseudomyxoma peritoneum (Pseudomyxoma peritonei, PMP) and hepatocellular carcinoma characterized by failure of standard treatment (disease progression or intolerance, such as chemotherapy, targeted therapy, and other immunotherapies) or patients who have no standard treatment or patients 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.

  1. 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.
  2. At least 1 measurable lesion according to RECIST 1.1 (for solid tumors).
  3. Patients have recovered from any toxic reaction to previous medications (≤Grade 1 based on NCI-CTCAE v 5.0, except a. Hair loss; b. Pigmentation; c. The long-term toxicity caused by radiotherapy and cannot be recovered by the investigator's judgment; d. Platinum induced neurotoxicity of grade 2 and below; e. Hemoglobin at 90 ~ 100 g / L (including boundary value)) or stable status assessed by the investigator.
  4. Eastern Co-Operative Oncology Group (ECOG) performance status 0 ~ 1 and a life expectancy of at least 3 months.
  5. Laboratory tests must meet the following requirements and have not received any blood cell growth factor 14 days before the test (Patients with laboratory values outside of the specified ranges will be permitted to be retested once in order to meet the criteria), rescreening for Hemoglobin, ALT, AST and coagulation function is allowed but only allowed once:
  6. absolute count of neutrophils (ANC) ≥1.5×109 /L, platelet ≥75×109 /L; Hemoglobin ≥90 g/L ;
  7. serum albumin ≥ 25g /L; Bilirubin ≤1.5 × ULN, ALT and AST ≤2.5 × ULN;
  8. In patients with liver metastasis, ALT and AST≤5 × ULN ;
  9. Creatinine clearance ≥50 mL/min (standard Cockcroft -Gault formula) or Cr ≤1.5 ×ULN: urinary protein ≥2+ or urinary protein quantitative <1.0 g/L
  10. International standardized ratio of coagulation function (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
  11. 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.
  12. Female patients of childbearing potential must agree to use acceptable method(s) of contraception from consent through at least 6 months after drug infusion.
  13. . Male patients of reproductive capacity must agree to use effective contraception from start of mobilization through at least 6 months after drug infusion
  14. . Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy (HBV DNA test is less than 2000 IU/ml) should be on a suppressive antiviral therapy prior to initiation of cancer therapy. Patients with a history of HCV infection should have completed curative antiviral treatment and HCV viral load below the limit of quantification. Patients with HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible. Patients on concurrent HCV treatment should have HCV below the limit of quantification.
  15. . Patients must be able to follow up after the treatment.
  16. . Patients must understand and voluntarily sign the informed consent form.

You CAN'T join if...

  • Patients will be excluded from participation for any of the following criteria:
  • Received systemic or absorbable dosage of steroid hormone (prednisone or equivalent) of >10 mg/day in the 14 days prior to enrollment;
  • Prednisone >10 mg/day
  • Dexamethasone >1.5 mg/day.
  • Currently using antibiotic.
  • Tumors in hollow organs (Stomach, esophagus, intestine, urinary tract etc.).
  • Present with symptomatic central nervous system metastasis or brain abscess at screening.
  • Present with diverticulitis or conditions at screening that might promote the unintentional growth of anaerobic bacteria in nontarget lesions.
  • Existing cardiac clinical symptoms or diseases that cannot be well controlled, such as:
  • NYHA grade 2 or above heart failure;
  • Unstable angina pectoris;
  • Myocardial infarction occurred within 1 year;
  • Patients with supraventricular or ventricular arrhythmias that have clinical significance and need treatment or intervention;
  • Uncontrolled hypertension (systolic blood pressure) ≥160 mmHg and (diastolic blood pressure) ≥100 mmHg after drug treatment;
  • Patients with valvular heart disease or mitral valve prolapse, aortic valve disease or other source of turbulent cardiac blood flow.
  • 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).
  • 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).
  • Positive for the presence of human immunodeficiency virus-1 (HIV-1) or human immunodeficiency virus-2 (HIV-2) (positive antigen/antibody and nucleic acid tests); or follow standard of care for HIV diagnosis.
  • . Patients with Anti-TP positive.
  • . 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.
  • . Vaccination within 28 days of the first trial treatment, except for administration of inactivated vaccines and RNA vaccines (e.g., inactivated influenza vaccines and COVID-19 RNA vaccines) ;
  • . Received live or attenuated vaccines within 4 weeks of study drug administration, during treatment, or within 5 months of the last administration.
  • . 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 patients or test data and sample collection.
  • . In the researcher's judgment, patients who are not suitable for other reasons.
  • . Documented salmonella infections within 6 months.
  • . Allergic to any study medications or rescue medications.
  • . Patients with implants such as pacemakers, prosthetic cardiac valves, or metal orthopedic prostheses.

Locations

  • Health Chao Family Comprehensive Cancer Center not yet accepting patients
    Orange California 92868 United States
  • Banner MD Anderson Cancer Center not yet accepting patients
    Gilbert Arizona 85234 United States

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
Guangzhou Sinogen Pharmaceutical Co., Ltd
ID
NCT05038150
Phase
Phase 1 Solid Tumor Research Study
Study Type
Interventional
Participants
Expecting 50 study participants
Last Updated