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

Advanced Solid Tumor Clinical Trial

Official title: A Phase I/IIa, Open-label, Dose Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Modified Salmonella Typhimurium SGN1 Administered Via Intratumoral Injection in Patients With Advanced Solid Tumors

Status Recruiting

Clinical Trial 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 at OBD doses.

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.

Clinical Trial 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 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/IIa clinical trial with 2 parts:

Part 1 is a phase I open-label, dose escalation study phase. The purpose of Part 1 is to characterize safety, tolerability, MTD and OBD of intratumoral injection of SGN1 in patients with advanced solid tumors. Part 2 is as a part of a phase Ib/IIa study, which is a specific Tumor-type expansion study, the purpose of Part 2 is to preliminarily investigate the efficacy and safety of SGN1 in specific tumor subtypes at Safety Monitoring Committee (SMC) determined doses.

SGN1 will be administrated in 28-days cycles (once weekly for 3 weeks followed by 1-week rest). Intratumoral injection of SGN1 can be performed 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 tumor can also be injected under CT guidance by an interventional radiologist or specialist with adequate qualifications and trainings. ;

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

• NCT number: NCT05103345
• Study type: Interventional
• Source: Guangzhou Sinogen Pharmaceutical Co., Ltd
• Contact: Garin Liu
• Phone: +886-(0) 905 891 942
• Email: Garin.Liu@parexel.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 19, 2023
• Completion date: June 30, 2028