NCT05038150

Study of SGN1 in Patients With Advanced Solid Tumor

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Guangzhou Sinogen Pharmaceutical Co., Ltd · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Objectives:To assess the safety and tolerability followed by a dose expansion study to characterize safety, and preliminary efficacy of SGN1 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.

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 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 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 DLT observation period. Part 3 is an open-label, dose expansion phase. 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 and cause stopping study drug for 2 planned administrations, 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. In part 3, there will be at least 2 tumor types selected, expand between second to four dose level in each tumor type.The Part 3 (Dose expansion stage study) could be started according to the SMC evaluation, do not need waiting the completion the whole cohort of dose escalation (Part 1).

Conditions

• Advanced Solid Tumor

Interventions

Type	Name	Description
DRUG	SGN1	The study drug, SGN1, will be administered as an IV infusion through a dedicated line catheter over 2 hours, which unit dose strength is 0.9-2.0×109 cfu /vial.

Timeline

• Start date: 2023-01-16
• Primary completion: 2028-01-18
• Completion: 2028-08-31
• First posted: 2021-09-08
• Last updated: 2025-04-30

Locations

8 sites across 2 countries: United States, China

Regulatory

• FDA-regulated drug study