Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase I Study of SGN1 in Patients With Advanced Solid Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05038150
Recruitment Status : Not yet recruiting
First Posted : September 8, 2021
Last Update Posted : September 8, 2021
Sponsor:
Information provided by (Responsible Party):
Guangzhou Sinogen Pharmaceutical Co., Ltd

Brief 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.


Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: SGN1 Phase 1

Detailed Description:

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 (VNP20009-M) 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.

The study will be conducted in 3 parts.The study will employ a standard 3 + 3 escalating dose design to explore dose limiting toxicities (DLTs) in up to 5 sequential cohorts with 3- 6 patients to determine the maximally tolerated dose (MTD). Subjects who had no dose-limiting toxicities observed in Part 1 proceeded to Part 2. In part 2, SGN1 will be administered weekly until disease progression, unacceptable toxicity, withdrawal, death, or loss to follow-up.After OBD and responsive tumor type been determined, up to 10 participants/tumor type will be dosed in the expansion stage.

Layout table for study information
Study Type : Interventional
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: The study will employ a standard 3 + 3 escalating dose design to explore dose limiting toxicities (DLTs) in up to 5 sequential cohorts with 3-6 patients to determine the maximally tolerated dose (MTD). Alternatively, if a DLT occurs in only 1/3 participants at any dose, then the SMC will review the data and determine if 3 more patients should be enrolled at this dose level. If this is the highest dose and there have been no DLTs-then 3 more participants must be evaluated at the same dose level to confirm the MTD. The MTD is defined as the highest dose at which not more than one (1) DLT is observed among 6 participants.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 31, 2021
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : January 31, 2024

Arm Intervention/treatment
Experimental: one arm
Cohorts of 3 participants will be enrolled, admitted to an infusion unit, and treated with a single IV infusion of SGN1 over 2 hours and closely evaluated for DLTs for 28 days after the infusion unit. Up to 5 cohorts will be evaluated.
Drug: SGN1
SGN1, will be administered as an IV infusion, via an IV catheter over 2 hours,which Unit Dose Strength is 0.9-2.0×109 cfu /vial.
Other Name: SalMet-Vec




Primary Outcome Measures :
  1. Incidence of clinician reported adverse events. [ Time Frame: from signing the informed consent form until 28 days after the last dose. ]

    An AE is any untward medical occurrence in a patient or clinical investigation subjects, temporally associated with the use of a medicinal product,whether or not considered related to the medicinal product.

    An AE can therefore be any unfavorable and unintened sign (including an abnormal laboratory finding),symptom,or disease(new or exacerbated)temporally associated with the use of a medicinal product.


  2. Objective response rate (ORR) [ Time Frame: from signing the informed consent form until 28 days after the last dose. ]
    Tumor response will be determined by the investigator according to RECIST Version 1.1. The endpoint includes ORR, DCR, PFS.

  3. Disease control rate (DCR) [ Time Frame: from signing the informed consent form until 28 days after the last dose. ]
    Tumor response will be determined by the investigator according to RECIST Version 1.1. The endpoint includes ORR, DCR, PFS.

  4. Progress Free Survival (PFS) [ Time Frame: from signing the informed consent form until 28 days after the last dose. ]
    Tumor response will be determined by the investigator according to RECIST Version 1.1. The endpoint includes ORR, DCR, PFS.


Secondary Outcome Measures :
  1. Incidence with any dose limiting toxicity (DLT),to determine the MTD. [ Time Frame: up to 28 days after the first administration. ]

    Any of the following judged to be associated with SGN1 (i.e., possibly-, probably-, or definitely related to), may be considered a DLT:

    1. Any Grade 5 adverse event that is at least possibly related to investigational drug
    2. Grade 4 non-hematological toxicities (excluding alopecia) of any duration
    3. Grade 3 non-hematologic (non-laboratory) toxicity lasting at least 7 days despite optimal supportive care
    4. Any Grade 3 non-hematologic laboratory value if: a) medical intervention is required to treat the patient; or b) the abnormality leads to hospitalization; or c) the abnormality persists for at least 7 days
    5. Grade 4 hematologic toxicity, other than those specified in criteria 6 and 7 below, lasting longer than 7 days
    6. Grade 3 or Grade 4 febrile neutropenia of any duration
    7. Grade 3 thrombocytopenia in combination with a Grade 3 or greater blood and lymphatic system disorder
    8. Grade 3 AST or ALT that is associated with a Grade 2 or greater rise in bilirubin.

  2. Incidence with adverse events and preliminary efficacy data to determine the OBD. [ Time Frame: Upon completion of 28-day observation periods in the cohort. ]
    OBD will be determined by adverse events, preliminary efficacy data,and the OBD determined by the SMC.

  3. Blood and tissue levels of SGN1 [ Time Frame: Pre-dose,30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 2 hours 20 minutes, 2 hours 40 minutes, 3 hours, 3 hours 30 minutes, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours after the start first and fifth dose. ]
    Peak and minimal SGN1 level in blood by culture.

  4. Proinflammatory cytokines [ Time Frame: Blood samples will be collected at 2, 4, 6, and 24 hours post first infusion to assess proinflammatory cytokines including IL-1β, TNF-α, IL6, and IL-12. ]
    Proinflammatory cytokines including IL-1β, TNF-α, IL-6, and IL-12

  5. Biodistribution and shedding of SGN1 [ Time Frame: Sampling for biodistribution and shedding will be conducted on days 1, 4, and 7 of first 2 week. ]
    SGN1 level in blood and urine. Shedding of SGN1 in oral mucosa, anogenital region samples, surface of injected site, exterior of occlusive dressings

  6. Incidence of AEs, SAEs, etc. [ Time Frame: from signing the informed consent form until 28 days after the last dose. ]
    To evaluate the safety of SGN1 in specific tumor subtypes


Other Outcome Measures:
  1. Tumor biomarkers [ Time Frame: from baseline until 28 days after the last dose. ]
    To explore the effect of SGN1 on tumor biomarkers.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05038150


Contacts
Layout table for location contacts
Contact: Alissa McGuire +1 919-259-4028 amcguire@ncgs.com
Contact: May Zuo +86 18618143241 may.zuo@clinchoice.com

Sponsors and Collaborators
Guangzhou Sinogen Pharmaceutical Co., Ltd
Layout table for additonal information
Responsible Party: Guangzhou Sinogen Pharmaceutical Co., Ltd
ClinicalTrials.gov Identifier: NCT05038150    
Other Study ID Numbers: SGN-P01-001
First Posted: September 8, 2021    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms