Evaluating Safety, Tolerability, and Preliminary Efficacy of YSCH-01 Monotherapy and in Combination With Atezolizumab for Recurrent Glioblastoma

An Open-Label, Single-Center, Multiple-Dose Exploratory Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of YSCH-01 Monotherapy and in Combination With Atezolizumab in the Treatment of Recurrent Glioblastoma

The clinical study of YSCH-01 will adopt an open-label, randomized design, with a planned enrollment of 10 participants with recurrent glioblastoma. Participants will be randomly allocated to the YSCH-01 monotherapy cohort or the YSCH-01 + Atezolizumab combination cohort, with 5 participants in each cohort. The study consists of the following three phases: screening phase, treatment phase, and follow-up phase. The primary endpoint is the 1-year survival rate of participants

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Biological: YSCH-01; Biological: Atezolizumab (1200 mg every three weeks)

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Shan Jiang, Dr.; Phone Number: +86 13661519863; Email: jsscosmos@gmail.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Recruiting
      • Huashan Hospital
      • Contact: Shan Jiang; Phone Number: +86-13661519863; Email: jsscosmos@gmail.com
      • Principal Investigator: Zhifeng Shi, Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

Participants must meet all the following criteria to be enrolled in this study:

1. Age > 18 years, male or female.
2. Expected survival ≥ 12 weeks.
3. Karnofsky Performance Status (KPS) score ≥ 70 at baseline.
4. Histopathologically confirmed glioblastoma (GBM), with first recurrence after prior surgery, chemotherapy, and/or radiotherapy.
5. Presence of 1 contrast-enhancing tumor lesion (diameter 1-4 cm) assessed by MRI during the screening phase.
6. Eligibility for tumor biopsy and Ommaya reservoir implantation based on hematological, hepatic, renal, and coagulation function parameters.
7. Recovery from toxic effects of prior chemo/radiotherapy (CTCAE ≤ Grade 1, except for special cases like alopecia or pigmentation), with the Investigator determining that the corresponding adverse events (AEs) pose no safety risk.
8. Eligible subjects of reproductive potential (male and female) must agree to use effective contraception during the trial and for at least 6 months after the last dose.

Exclusion Criteria

Participants with any of the following conditions are ineligible for enrollment:

1. History or current evidence of another primary malignancy.
2. Known allergy to the study drug or any of its excipients, or a history of unexplained severe allergic reactions.
3. Any contraindication to gadolinium-enhanced MRI, such as presence of a pacemaker, infusion pump, or allergy to MRI contrast agents.
4. Tumor involvement of the brainstem, cerebellum, or spinal cord; or leptomeningeal disease.
5. MRI evidence of tumor enhancement extending to the ventricular wall, or the tumor cavity is fused with the ventricle after surgery.
6. Preoperative MRI assessment showing the Ommaya puncture path traverses the ventricles.
7. Active infection requiring intravenous antibiotic therapy, or unexplained fever (body temperature ≥37.5°C).
8. Uncontrolled systemic diseases or relevant medical history, including: diabetes mellitus, cardiovascular/cerebrovascular disease (e.g., heart failure ≥NYHA Class II, hypertension ≥Grade 2, ≥First-degree atrioventricular block, history of myocardial infarction, myocarditis), pulmonary insufficiency, thyroid dysfunction, cerebral infarction within the past 6 months.
9. Active autoimmune disease or history of autoimmune disorders (e.g., ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitis, Wegener's granulomatosis).
10. Plan or requirement to receive any live vaccine during the screening or treatment phase.
11. Other conditions assessed as incompatible with intravenous administration of Atezolizumab.

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: YSCH-01 monotherapy; Participants will receive YSCH-01 monotherapy administered via intratumoral or intratumoral cavity injection through an implanted Ommaya reservoir.	Biological: YSCH-01; Participants will receive YSCH-01 monotherapy at a dose of 5.0 × 10¹⁰ VP every 3 weeks. YSCH-01 will be administered via intratumoral or intracavitary injection through an implanted Ommaya reservoir.
Experimental: YSCH-01 in combination with Atezolizumab; Participants will receive YSCH-01 in combination with atezolizumab. YSCH-01 will be administered via intratumoral or intratumoral cavity injection through an implanted Ommaya reservoir, and atezolizumab will be administered intravenously.	Biological: YSCH-01; Participants will receive YSCH-01 monotherapy at a dose of 5.0 × 10¹⁰ VP every 3 weeks. YSCH-01 will be administered via intratumoral or intracavitary injection through an implanted Ommaya reservoir.; Biological: Atezolizumab (1200 mg every three weeks); Participants will receive YSCH-01 in combination with atezolizumab every 3 weeks. YSCH-01 will be administered via intratumoral or intratumoral cavity injection through an implanted Ommaya reservoir on Day 1 of each cycle at a dose of 5.0 × 10¹⁰ viral particles (VP). Atezolizumab (PD-L1 inhibitor) will be administered via intravenous infusion on Day 8 of each cycle at a dose of 1200 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Nature of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Type, frequency, severity, and relationship to study treatment of AEs and SAEs assessed per NCI-CTCAE v5.0	From first dose up to 28 days after last dose
1-year survival rate	Defined as the proportion of participants who are alive at 1 year from the first dose of study intervention, referred to as 1-year Overall Survival (OS)	One year after receiving the first dose of YSCH-01

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai Yuansong Biotechnology Co., LTD
• Investigators: Principal Investigator: Zhifeng Shi, Dr., Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2025
• Primary Completion (Estimated): November 27, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Recurrent Glioblastoma; Atezolizumab; Adenovirus; YSCH-01
• Additional Relevant MeSH Terms: Neoplasms; Infections; Virus Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; DNA Virus Infections; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Adenoviridae Infections; atezolizumab
• Other Study ID Numbers: KY2024-1142

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No