Study of MT027 in Patients with Recurrent or Progressive High-grade Glioma

A Single-arm, Dose-escalation Phase I Clinical Study on Evaluating the Tolerability, Pharmacokinetic Characteristics, Safety and Preliminary Efficacy of MT027 in Patients with Recurrent or Progressive High-grade Glioma

The clinical protocol plans to preset three dose groups, namely 1×10⁷ cells per dose, 3×10⁷ cells per dose, and 6×10⁷ cells per dose. The injection will be administered once every three weeks, adopting a "3 + 3" dose escalation design. The dosing interval is based on the pharmacokinetic (PK), safety and preliminary efficacy data of MT027 investigator-initiated trial (IIT) previously conducted at Dushu Lake Hospital of Soochow University. Accordingly, it is recommended to maintain the dosing interval of once every three weeks, with a window period of ±7 days. According to past experience, the dosing cycle should be at least 6 cycles, with each cycle lasting 21 days. If patients still benefit after more than 6 cycles, they can continue to receive the medication until no further benefit is achieved. The number of treatment sessions is approximately 6 to 9 times. However, the specific number of treatment sessions will generally be determined by the investigator based on the patient's disease condition.

Study Overview

• Status: Not yet recruiting
• Conditions: High-grade Glioma
• Intervention / Treatment: Drug: MT027 cells suspension

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Guangyuan Hu; Phone Number: +86-027-83663405; Email: h.g.y.121@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
      • Contact: Guangyuan Hu; Phone Number: +8602783663405; Email: h.g.y.121@163.com
      • Contact: Lei Huang; Phone Number: +8615962138334; Email: huanglei@t-maximum.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily participate in this study and sign the informed consent form.
2. Be aged between 18 and 70 years old (including the critical values), with no gender limitation.
3. Subjects with high-grade glioma diagnosed pathologically (referring to grade 3 or 4 in the "WHO (2021) Classification of Tumors of the Central Nervous System"), who have progressive disease during standard treatment or have recurrence after standard treatment.
4. Enhanced MRI shows space-occupying lesions in the brain, and there is at least one measurable lesion (according to the iRANO 2010 version criteria).
5. The tumor tissue of the patient has positive expression of B7-H3. The subject voluntarily provides the most recent formalin-fixed paraffin-embedded (FFPE) tissue or pathological sections (at least 8 consecutive blank sections) for the detection of B7-H3 expression (immunohistochemistry, IHC).
6. Have an expected survival period of ≥ 3 months.
7. Have a Karnofsky Performance Scale (KPS) score of ≥ 70 points. -

Exclusion Criteria:

1. Patients with recurrence in the brainstem, spinal cord dissemination or extracranial metastasis; 2. The maximum diameter of a single tumor lesion is > 5 cm, or the cumulative maximum diameter of multiple lesions is > 6 cm; 3. Having received radiotherapy within 3 months before cell therapy or having received surgical treatment (except for Ommaya reservoir implantation), chemotherapy (except for lymphocyte depletion therapy), immunotherapy, molecular targeted therapy or any other anti-tumor therapy within 4 weeks before cell therapy; 4. Having participated in other drug clinical trials within 4 weeks before screening; 5. Having previously received CAR-T cell therapy; 6. Subjects with a severe allergy history to any component of the experimental drug or biological products; 7. Subjects with other primary malignancies (except for cured cervical carcinoma in situ and basal cell carcinoma of the skin); 8. Suffering from major diseases such as active systemic infection and coagulation disorders; 9. Suffering from severe insufficiency of heart, lung, liver and kidney functions; cardiac function: grade III or above according to the New York Heart Association (NYHA) criteria; liver function: grade C or above according to the Child-Pugh grading criteria; renal function: chronic kidney disease (CKD) stage 4 or above; renal insufficiency stage III or above; pulmonary function: severe respiratory failure symptoms involving other organs; 10. Subjects with severe autoimmune diseases; 11. Subjects who have previously received allogeneic tissue/solid organ transplantation; 12. Subjects who have received live vaccines within 2 weeks before the first cell therapy or who plan to receive live vaccines during the study period; 13. Subjects with active hepatitis B virus infection; or patients with hepatitis C virus infection (defined as positive HCV antibody, and those with HCV-RNA below the detection limit are allowed to enroll); or patients with human immunodeficiency virus infection (defined as positive HIV antibody); or patients with positive treponema pallidum antibody; 14. Having symptoms and signs of epilepsy or chronic intracranial hypertension that are difficult to control with drugs (for example, those using more than 500 ml of mannitol or more than 15 mg of dexamethasone or more than 80 mg of methylprednisolone or other hormones in equivalent doses per day); 15. Subjects judged by the investigator to have severe neurocognitive disorders; 16. Pregnant or lactating women; 17. Those who are considered by the investigator to be unsuitable for participating in this clinical study due to any clinical or laboratory examination abnormalities or other reasons.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MT027	Drug: MT027 cells suspension; MT027: CRISPR/Cas9 edited B7H3-specific allogeneic CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Limiting Toxicity (DLT)	28 days
GvHD	through study completion, an average of 1 year
CRS	through study completion, an average of 1 year
Immune effector cell-associated neurotoxicity syndrome (ICANs)	through study completion, an average of 1 year
Adverse Events (AE) and Serious Adverse Events (SAE)	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Suzhou Maximum Bio-tech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: High-grade glioma; MT027
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: MT027-HGG-002

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
• product manufactured in and exported from the U.S.: No