Phase I/IIa, Open-label Study to Evaluate Safety, Tolerability and Preliminary Efficacy of Modified Salmonella Typhimurium SGN1 in Patients With Advanced Solid Tumor
Guangzhou Sinogen Pharmaceutical Co., Ltd
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.
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 expres…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria Patients 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 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 p…
Interventions
- DrugSGN1
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.
Locations (8)
- Banner MD Anderson Cancer CenterGilbert, Arizona
- Health Chao Family Comprehensive Cancer CenterOrange, California
- Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer CenterDetroit, Michigan
- University of Cincinnati Cancer CenterCincinnati, Ohio
- Guangdong Clifford HospitalGuangzhou, Guangdong
- Harbin Medical University Cancer HospitalHarbin, Heilongjiang