A Phase I, Single-arm, Open-label Clinical Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of CHT101 Cell Infusion in Adult Subjects With Recurrent or Progressive Malignant Primary Brain Tumors（CROWN）

Official title

A Phase I, Single-arm, Open-label Clinical Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of CHT101 Cell Infusion in Adult Subjects With Recurrent or Progressive Malignant Primary Brain Tumors

Overview

Recurrent or progressive primary malignant brain tumors are among the malignancies with a poor prognosis. They refer to primary brain tumors that either recur after standard treatment or show disease progression during the course of standard therapy. This group includes a variety of histological types, most commonly glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, and primary central nervous system lymphoma.

Interventions

• Biological CHT 101
  CHT101 is an allogeneic CD70-targeted chimeric antigen receptor Tcell therapy, intended to be administered locally for the treatment of primary malignant brain tumors.

Primary outcome measures

• Safety and Tolerability [Time frame: 2 years]

Secondary outcome measures (5)

• Objective response rate (ORR) [Time frame: 2 years]
• Progress-free survival(PFS) [Time frame: 2 years]
• Overall survival (OS ) [Time frame: 2 years]
• pharmacokinetics (PK) [Time frame: 2 years]
• Pharmacodynamics (PD) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Tumor tissue specimens must be CD70-positive as determined by immunohistochemistry (IHC).

Subjects must be pathologically confirmed to have high-grade glioma, defined as WHO (2021) Central Nervous System Tumor Classification grade 3 or 4 gliomas; or primary central nervous system lymphoma (PCNSL).

Contrast-enhanced magnetic resonance imaging (MRI) must demonstrate the presence of an intracranial space-occupying lesion, with at least one measurable lesion.

At the time of signing the informed consent form (ICF), the Karnofsky Performance Status (KPS) score must be ≥70.

Exclusion criteria

• Patients with brainstem recurrence, spinal dissemination, or extracranial metastasis.

History of bone marrow or solid organ transplantation. History of other primary malignancies within 5 years prior to study treatment. Prior receipt of CD70-targeted antitumor therapies, including but not limited to CD70-targeted cell therapies (autologous or allogeneic) and TCR-T therapy.

Prior treatment with CAR-T therapy or other cell/gene therapies. Presence of acute or moderate-to-severe chronic graft-versus-host disease (GVHD) within 4 weeks prior to signing the informed consent form (ICF), or receipt of systemic therapy for GVHD within 4 weeks prior to the first infusion.

Clinically significant cardiovascular disease. Epilepsy that is difficult to control with medication, or chronic symptoms and signs of intracranial hypertension.

Inadequate bone marrow reserve or organ function. Pregnant or breastfeeding female subjects.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07496073 · CHT101SIIT-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗