First in Human Study of YB1-X7 Injection

An Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of YB1-X7 Injection in Subjects with Advanced Solid Tumors

This clinical trial is an open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetic, and preliminary efficacy of YB1-X7 injection in subjects with advanced solid tumors.

YB1-X7 injection is an attenuated Salmonella-based tumor therapy. It selectively accumulates in hypoxic tumor regions while being rapidly cleared from normal organs. After proliferating in the tumor microenvironment, YB1-X7 invades tumor cells and releases its therapeutic payload, leading to tumor cell death and tumor regression.

Conditions：To treat subjects with advanced and/or metastatic solid tumors who do not to respond to conventional standard treatment or who lack effective standard treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: YB1-X7 Injection (IT); Drug: YB1-X7 Injection (IV)

Detailed Description

YB1-X7 is a genetically engineered attenuated Salmonella enterica strain. It has been further optimized based on the attenuated model of VNP20009 while inserting an anaerobic-targeting enrichment system, transforming YB1-X7 into a nutrient-deficient strain under aerobic conditions. This modification allows YB1-X7 to selective proliferation in hypoxic tumor regions while being cleared in normal oxygenated tissues, thereby achieving selective enrichment in tumor.

Additionally, YB1-X7 carries plasmids encoding the drug protein. Upon reaching the tumor region, YB1-X7 invades tumor cells, expressing and releasing drug protein, leading to tumor cell death and tumor regression.

This study is divided into two parts based on the route of administration:

Part 1: Subjects receiving intratumoral injection (IT). Part 2: Subjects receiving intravenous infusion (IV).

Both administration routes will have three dose cohorts (low, medium, and high dose) following the standard 3+3 dose-escalation design, with single-dose multiple administrations in an escalating dose scheme.

Each subject will receive only one administration method (IT or IV) and be assigned to only one dose cohort, completing the full treatment regimen for that dose level.

YB1-X7 injection will be administrated in 28-days cycles (once weekly for 3 weeks followed by 1-week rest).

For Subjects receiving intratumoral injection, superficial lesions can be injected directly, while deep-seated lesions may require ultrasound, CT, or endoscopic guidance for precise administration.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years, no gender limitatlon
2. Subjects with advanced or metastatic solid tumors confirmed by pathological histology.
3. Subjects with advanced malignant solid tumors for whom standard treatment has failed or no other effective standard treatment available.
4. At least one measurable solid tumor by RECIST 1.1.
5. Subjects assigned to intratumoral injection must have at least one tumor that is suitable for biopsy or intratumoral injection.
6. Life expectancy must be at least 3 months.
7. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.

8. Male and female subjects of childbearing potential should take effective contraceptive measures.

   ① Fertile women and men must agree to use acceptable contraceptive methods from the start of informed consent until at least 6 months after the last administration.

9. Laboratory blood test results during the screen period:

(1)No blood cell growth factors received within 14 days prior to testing.

① Absolute neutrophil count (ANC)≥1.5×109/L.

② Platelets≥90×109/L. Hemoglobin ≥90 g/L (blood transfusion is allowed to correct). (2) Serum albumin >30 g/L, total bilirubin <1.5×ULN, ALT and AST <2.5×ULN; for subjects with liver metastasis, ALT and AST <5×ULN; creatinine clearance ≥50 mL/min (Cockcroft-Gault formula) or Cr <1.5×ULN; (3) Prothrombin time (PT) and activated partial thromboplastin time (aPTT) <1.5×ULN.

10. Subjects understand the study and willing to sign the informed consent form.

Exclusion Criteria:

1.Pregnant or breastfeeding women. Subjects known to have a history of abuse of psychiatric drugs, alcoholism, or drug use.

3.Subjects who have previously undergone oncolytic bacteria treatment. 4.Subjects planning to surgery, radiation therapy, or other local treatments for target lesions during the study.

5.Subjects known to be allergic to the study drug or any of its excipients. 6.Subjects allergic or intolerant to antibiotics sensitive to Salmonella, such as amikacin cefpirome, ciprofloxacin,cefotaxime,meropenem.

7.Subjects currently using antibiotics. 8.Subjects who have not recovered fom adverse reactions of prior treatments (treatment-related toxicity grade≤2, except for hair loss, pigmentation, and other tolerable events determined by the investigator).

9.Subjects with active auto-immune diseases or prior diseases with recurrence potential (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroiditis.

10.Subjects with active or uncontrolled infections or unexplained fever≥38.5℃, including but not limited to bacterial infections, tuberculosis, herpes virus infections syphilis infections.

11.Subjects who underwent major surgery within 3 months prior to the first dose of the study drug (except for biopsies for diagnostic purposes).

12.Subjects who have received any anti-tumor treatment within 28 days or 5 half-lives prior to the first dose of the study drug, including chemotherapy, cell therapy, gene therapy, immunotherapy,biological agents, hormone therapy, targeted therapy, tumor drug embolization therapy.

13.Subjects who received radiation therapy within 28 days prior to the first dose of the study drug (except for local radiation therapy for pain relief).

14.Subjects who receive (live attenuated) virus vaccines: within 28 days prior to the first dose of the study drug, or during the study period or within 60 days after the last dose of the study drug.

Subjects who have used immunosuppressive drugs within 14 days prior to the first dose of the study drug (i.e., prednisone≥10 mg/day, dexamethasone≥1.5 mg/day), except for corticosteroid nasal sprays and inhaled corticosteroids or physiological doses of systemic corticosteroids (i.e., prednisone not exceeding 10 mg/day)or equivalent physiologica doses of other corticosteroids.

16. Subjects with known, uncontrolled, or symptomatic active central nervous system conditions.

17. Subjects with existing clinical symptoms or pooely controlled heart disease:

1. New York Heart Association (NYHA) class ≥II;
2. Unstable angina;
3. Myocardial infarction within the past year; Subjects with clinically significant supraventricular or ventricular arrhythmias needing treatment or intervention; Medicaion uncontrolled hypertension or hypotension (determined by the investigator); Subjects with valvular heart disease or mitral valve prolapse, aortic valve disease; Severe myocardial diseases. 18.Subjects known to have peripheral thromboembolic vascular diseases, aneurysms, or arterial/venous malformations.

19.Subjects Known allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

20.Subjects who are positive for Treponema pallidum antibodies, individuals with human immunodeficiency virus (HIV) infection, or known acquired immunodeficiency syndrome (AIDS).

21.Subjects with active hepatitis B (HBsAg positive and/or HBcAb positive with HBV-DNA ≥2000 IU/mL or requiring antiviral treatment), or those who test positive for hepatitis C virus (HCV) antibodies; or subjects co-infection with hepatitis B and C.

22.Other reasons unsuitable for the study as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YB1-X7 Injection Intratumoral Injection; YB1-X7 injection will be injected into the target lesion intratumorally. Three cohorts (low, medium, and high) will be assigned. The standard 3+3 dose-escalation design will be applied to explore dose limiting toxicity in 3 sequential cohorts with 3- 6 patients.	Drug: YB1-X7 Injection (IT); Intratumoral injection; Other Names: YB1-X7
Experimental: YB1-X7 Injection Intravenous Infusion; YB1-X7 injection will be administered as an IV infusion through a dedicated line catheter over 2 hours.Three cohorts (low, medium, and high) will be assigned. The standard 3+3 dose-escalation design will be applied to explore dose limiting toxicity in 3 sequential cohorts with 3- 6 patients.	Drug: YB1-X7 Injection (IV); Intravenous infusion; Other Names: YB1-X7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLTs)	DLT is defined as any toxic reaction associated with the study drug occurring within 28 days after the first administration, graded refer to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0).	Up to 28 days post first dose.
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.	From receiving study drug and throughout the study, until 28 days after the last dosing
Serious adverse events(SAEs)	A serious adverse event (SAE) refers to any medical event that results in: DeathLife-threatening conditions ③ Permanent or severe disability or loss of function④ Hospitalization or prolonged hospitalization⑤ Congenital abnormalities or birth defects Other important medical events, which may not immediately threaten life, death, or require hospitalization, but still necessitate medical interventions to prevent one of the above outcomes, are also considered serious. Examples include: Urgent treatments in an emergency roomAllergic bronchospasm (even if not requiring hospitalization) ③ Severe cachexia or seizures ④ Drug dependence or addiction Death due to drug-related adverse events (e.g., ventricular fibrillation) is classified as an SAE. However, if the death is due to the progression of the underlying disease (e.g., cancer) and the adverse event was mild (e.g., a rash or abdominal pain), it is not considered an SAE.	From receiving study drug and throughout the study, until 28 days after the last dosing.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
YB1-X7 level in blood for PK analysis	Evaluate the drug concentration and pharmacokinetics for subjects in different dose groups after the dose of either intratumoral injection or intravenous infusion.	Before the first administration up to 28 days after the last dosing.
Immunogenicity (anti-drug antibodies)	The changes in the levels of anti-YB1-X7 antibodies (ADA) will be evaluated at different time points.	Before the first administration up to 28 days after the last dosing.
YB1-X7 level in blood for bacterial shedding.	For subjects receiving intratumoral injection or intravenous infusion, blood samples will be collected in different dose groups.	Before the first administration up to 28 days after the last dosing.
YB1-X7 shedding level analysis in urine, saliva, faeces using qPCR	For subjects receiving intratumoral injection or intravenous infusion, samples will be collected in different dose groups, including urine, saliva and faeces (or rectal swab), and the shedding level will be analysed using quantitative polymerase chain reaction (qPCR).	Before the first administration up to 28 days after the last dosing.
Cytokines	Changes in cytokines in the blood at different time points. Cytokines including IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α.	Before the first administration up to 28 days after the last dosing.
Objective Response Rate (ORR)	ORR represents the proportion of subjects with complete or partial response, assessed using RECIST 1.1 criteria based on imaging.	From signing the informed consent form until 28 days after the last dose.
Progression Free Survival (PFS)	PFS is defined as the time interval from date of first dose of YB1-X7 injection 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.
ime to Progression (TTP)	Time to Progression (TTP) is defined as the time from the start of treatment to the objective progression of the tumor.	From signing the informed consent form until 28 days after the last dose.
Duration of Response (DOR)	Duration of Response (DOR) is defined as the time from the first assessment of Complete Response (CR) or Partial Response (PR) until Disease Progression (PD). It represents the duration that the tumor remains reduced following the treatment.	From signing the informed consent form until 28 days after the last dose.
Overall Survival (OS)	OS will be evaluated for subjects in different dose groups who received intratumoral injection or intravenous infusion at Week 52 (1 year). Overall Survival (OS) is defined as the time from the start of treatment to death from any cause.	1 year
ECOG Performance Status Before and After Treatment	Changes in ECOG performance status will be assessed for subjects in different dose groups who received intratumoral injection or intravenous infusion compared to baseline. The score will refer to the Eastern Cooperative Oncology Group (ECOG) Performance Status.	From baseline to week 12

Collaborators and Investigators

• Sponsor: Shanghai Salvectors Biotechnology LTD.

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: ZXK24-D1-P001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to confidentially and regulatory reasons

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No