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

NCT05103345 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SGN-P01-002
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 4

Brief Summary

Objectives: To characterize safety, tolerability, MTD and OBD of intratumoral injection of SGN1 in patients with advanced solid tumors, and to preliminarily investigate the efficacy and safety of SGN1 in specific tumor subtypes. 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 presenting with histologically confirmed advanced and/or metastatic solid tumors that are refractory to standard therapy and for which no other conventional therapy exists.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events (AEs)

  An AE is any untoward medical occurrence in a patient or clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Events meeting the definition of an AE include: * Any abnormal laboratory test results (hematology, serum chemistry, or urinalysis) or other safety assessments (e.g., ECGs, vital signs measurements), including those that worsen from baseline, and was felt to be clinically significant in the medical and scientific judgment of the Investigator. * Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency and/or intensity of the condition. * New conditions detected or diagnosed after study treatment administration even though it may have been present prior to the start of the study. * Signs, symptoms, or the clinical sequelae of a suspected interaction.

  From receiving study drug and throughout the study, until 28 days after the last dosing

• Incidence of SAEs

  An AE or suspected adverse reaction is considered "serious" if it results in any of the following outcomes: * Death * Life-threatening * In patient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * A congenital anomaly/birth defect * Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.

  From receiving study drug and throughout the study, until 28 days after the last dosing

• Objective response rate (ORR)

  The efficacy endpoints include ORR, DCR and PFS. • The ORR is defined as the proportion of patients who achieve PR or better according to the RECIST v1.1. mRECIST is used to assess Hepatocellular carcinoma only, Choi criteria is used for all solid tumors, during the whole study, as the only exploratory tumor assessment method in the study, and LYRIC is used to assess Lymphoma as assessed by the investigator.

  From signing the informed consent form until 28 days after the last dose.

• Disease control rate (DCR)

  The efficacy endpoints include ORR, DCR and PFS. • The DCR is defined as the proportion of patients who achieve SD or better according to the RECIST v1.1, mRECIST is used to assess Hepatocellular carcinoma only, Choi criteria is used for all solid tumors, during the whole study, as the only exploratory tumor assessment method in the study, and LYRIC is used to assess Lymphoma as assessed by the investigator.

  From signing the informed consent form until 28 days after the last dose.

• Progression Free Survival (PFS)

  The efficacy endpoints include ORR, DCR and PFS. • PFS is defined as the time interval from date of first dose of SGN1 to the date of documented disease progression (iRECIST is used when the patient is suspected to be pseudo disease progression) or death due to any cause, whichever occurs first.

  From signing the informed consent form until 28 days after the last dose.

Secondary Outcomes (9)

• Incidence of dose limiting toxicity (DLTs)

  Up to 28 days post first dose

• SGN1 level in blood for PK analysis

  Before and after SGN1 injection in the first two cycles in Part 1 and Part 2.

• Immunogenicity (anti-drug antibodies)

  Before and after SGN1 injection in the first 4 cycles in Part 1 and Part 2.

• SGN1 level in blood for bacterial shedding.

  Before the first administration up to 28 days after the last dosing.

• SGN1 level in urine for bacterial shedding.

  Before the first administration up to 28 days after the last dosing.

Other Outcomes (1)

• Expression changes of tumor immune microenvironment related indicators in tumor tissue

  From signing the informed consent form until 28 days after the last dose.

Study Arms (1)

Cohort

OTHER

SGN1 will be injected into the target lesion intratumorally. According to the dose levels, the administered dose will be 0.5×108 CFU, 1×108 CFU, 2×108 CFU, 4×108 CFU, 6×108 CFU (optional). The patient will be administered once every week for 3 consecutive weeks followed by 1-week rest in 28-day treatment cycles. The duration of administration is until isease complete response/inability to continue intratumoral administration or disease progression, or intolerable toxicity or death or voluntary withdrawal or end of study, whichever came first. The standard 3+3 dose escalation algorithm will be applied to explore dose limiting toxicity (DLTs) in at least 4 sequential cohorts with 3- 6 patients and identify the maximally tolerated dose (MTD). When the cohort is completed in Part 1, the Part 2 study could be started according to the SMC evaluation. Enrollment of 2-4 dose level expansions will be opened to determine the safety and efficacy of SGN1 in specific tumor types

Drug: SGN1

Interventions

SGN1 DRUG

SGN1,will be administered intratumorally,which dosage is 0.9-2.0×109 cfu /vial.

Also known as: SalMet-Vec

Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be enrolled in the study, patients who have laboratory values outside of the specified ranges will be permitted to be retested. Patients who meet the following criteria at the screening visit will be eligible for participation in the study:
• Male or female aged 18\~75 years((including 18 and 75 years)) at the time of informed consent;
• Part 1: Patients with advanced stage (unresectable or metastatic) solid tumors 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 intolerable to standard treatment; Note: For all tumor species included, standard treatment will refer to current Chinese Society of Clinical Oncology (CSCO)/National Comprehensive Cancer Network (NCCN) guidelines.
• Standard treatment failure refers to patients who have disease progression after the existing standard of care recommended by CSCO/NCCN guidelines, or relapse/metastasis after standard of care.
• Non-standard treatment refers to patients who have received the treatment recommended by the guidelines and currently have no other effective treatment options.
• Part 2: the specific tumor-type expansion study may enroll the following patients: Patients with advanced HNSCC, Sarcoma, HCC, cervical cancer, melanoma, or other tumor type with potential efficacy signal observed in Part 1, who have failed to standard therapy or who are intolerant to the standard treatment.
• Patients must have the main lesion suitable for local injection of SGN1. The tumors must be in situ or metastatic solid tumors that are subcutaneous, palpable, or can be injected directly using methods including but not limited to color doppler ultrasound guidance, which is the preferred method. If the Investigator(s) judge(s) it necessary, the intratumoral injection can also be performed under CT guidance 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 previous imaging studies and Investigator assessment (no risk of major bleeding or hollow organ perforation).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Life expectancy ≥ 12 weeks.
• Patients have recovered from any toxic reaction to previous medications (≤Grade 1 based on NCI-CTCAE v 5.0, except
• Hair loss;
• Pigmentation;
• The long-term toxicity caused by radiotherapy and cannot be recovered by the Investigator's judgment;
• Platinum induced neurotoxicity of grade 2 and below;
• Hemoglobin at 90 \~ 100 g/L (including boundary value) or stable status assessed by the Investigator.

You may not qualify if:

• Patients will be excluded from participation of the study for any of the following criteria:
• Prior treatment with oncolytic bacteria viral or anti-tumor bacteria therapy.
• Patients with extremely large tumor (the longest diameter of a single tumor does not exceed 8 cm in principle); patients with multiple lesions cannot receive intratumoral injection, it mainly refers to patients with extensive metastasis who are not suitable for local treatment;
• Patients who are allergic or intolerant to salmonella sensitive antibiotics, and have infectious diseases and are currently using antibiotics.
• Present assessable tumors in hollow organs (stomach, esophagus, intestine, urinary tract etc.).
• Patients who are known to be allergic to the investigational drug or any of its excipients; or rescue medications; or have a severe allergic reaction to other monoclonal antibodies.
• Patients who have received the following treatments or drugs before the first treatment with the investigational drug:
• Major surgery performed within 28 days before the first treatment with the investigational drug (biopsy is allowed for diagnostic purposes);
• Immunosuppressive drugs have been administered within 14 days before the first treatment with the investigational drug (Prednisone \>10 mg/day, or equivalent doses of corticosteroids), 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);
• 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; Except for administration of inactivated vaccines and RNA vaccines (e.g., inactivated influenza vaccines and COVID-19 RNA vaccines);
• 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).
• Patients 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.
• Present with diverticulitis that may cause anaerobic bacteria to multiply or conditions at screening that might promote the unintentional growth of anaerobic bacteria in nontarget lesions.
• 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);
• 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 \[only patients whose condition can be controlled by hormone replacement therapy can be included\]; Patients 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);

Sponsors & Collaborators

• Pharmaron: collaborator
• Guangzhou Sinogen Pharmaceutical Co., Ltd: lead

Study Sites (4)

Guangdong Clifford Hospital

Guangzhou, Guangdong, 511495, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Taipei Medical University-Shuang Ho Hospital,Ministry of Health and Welfare

New Taipei City, 23561, Taiwan

RECRUITING

China Medical University Hospital

Taichung, Taiwan

RECRUITING

Central Study Contacts

Yifan Xu

CONTACT

(+86)18516560587; yifan.xu2@pharmaron.com

Weiyun Jia

CONTACT

(+86) 13810385484; Weiyun.Jia@pharmaron.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be conducted in 2 parts: Part 1 is a phase I open-label, dose escalation study phase. Part 2 is as a part of a phase Ib/IIa study, which is a specific Tumor-type expansion study. The standard 3+3 dose escalation algorithm will be applied to explore dose limiting toxicity (DLTs) in at least 4 sequential cohorts with 3- 6 patients and identify the maximally tolerated dose (MTD). When the cohort is completed in Part 1, the Part 2 study could be started according to the SMC evaluation.

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: November 2, 2021
• Study Start: April 19, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (2); CN (2)