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

Fudan University

Status and phase: Enrolling; Early Phase 1

Conditions: Recurrent Glioblastoma

Treatments: Biological: YSCH-01; Biological: Atezolizumab (1200 mg every three weeks)

Study type: Interventional

Funder types: Other

Identifiers

NCT07538128

KY2024-1142

Details and patient eligibility

About

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

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

YSCH-01 monotherapy

Experimental group

Description:

Participants will receive YSCH-01 monotherapy administered via intratumoral or intratumoral cavity injection through an implanted Ommaya reservoir.

Treatment:

Biological: YSCH-01

YSCH-01 in combination with Atezolizumab

Experimental group

Description:

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.

Treatment:

Biological: Atezolizumab (1200 mg every three weeks)

Biological: YSCH-01