A Phase II, Open-Label, Multicenter Study With a Safety Run-In to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of MT027 Administrated Intracerebroventricularly in Patients With Recurrent or Progressive Glioblastoma (WHO Grade 4)
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- T-MAXIMUM Pharmaceutical Inc
- Enrollment
- 40
- Locations
- 4
- Primary Endpoint
- Incidence rate of Dose-limiting toxicity (DLT)
Overview
Brief Summary
This is a Phase II trial to evaluate the safety, tolerability, efficacy, and PK/ pharmacodynamic profiles of MT027 injected via ICV in participants with recurrent or progressive IDH-wildtype glioblastoma (WHO 2021 CNS Grade 4), who have previously received standard of care (SOC) therapy.
Each participant will undergo screening, treatment (receiving MT027 at a dose of 3×10^7 cells), safety follow-up, and long-term follow-up periods.
MT027 will be given via ICV injection on Day 1 & Day 15 of the first 28-day cycle. If the participant does not experience any unacceptable toxicities and disease progress in the first cycle, additional treatment may be continued bi-weekly in a 28-day cycle (Days 1 & Day 15 of the 28-day cycle) until intolerable toxicity, disease progression, withdrawal from the study, or death, whichever comes first. After the last dose, there will be a safety follow-up period lasting for 1 year and then a long-term follow-up up to 15 years.
Detailed Description
This is a Phase II trial to evaluate the safety, tolerability, efficacy, and PK/ pharmacodynamic profiles of MT027 injected via ICV in participants with recurrent or progressive IDH-wildtype glioblastoma (WHO 2021 CNS Grade 4), who have previously received standard of care (SOC) therapy.
The study will begin with a safety run-in of 3 to 6 participants to evaluate the safety and tolerability of MT027 at a dose of 3×10^7 cells. Once the DLT assessment is complete, an additional 34 participants will be enrolled, bringing the total to 40, to evaluate the treatment's efficacy. Each participant will undergo screening, treatment, safety follow-up, and long-term follow-up periods. Any participant who has discontinued from study treatment other than disease progression will also continue to have tumor assessments until disease progression, initiation of subsequent anticancer therapies, withdrawal from the study, or death, whichever comes first. Upon completion of the safety follow-up, all patients, except those who died, withdrew consent, or were lost to follow-up, will enter to the long-term follow-up. It is regarded as the end of the study when the last participant has completed the 1-year long-term follow-up, or all participants have progressed, died, or lost to follow-up, whichever comes first. MT027 will be given via ICV injection on Day 1 & Day 15 of the first 28-day cycle, and the DLT observation period will be 28 days following the first dose of the first cycle (only for safety run-in group). After the DLT observation period, if the participant does not experience any unacceptable toxicities and disease progress, additional treatment may be continued bi-weekly in a 28-day cycle (Days 1 & Day 15 of the 28-day cycle) until intolerable toxicity, disease progression, withdrawal from the study, or death, whichever comes first. When confirming disease progression, the study treatment may still be continued if there's a potential for benefit, based on PI's discretion and the participant's willingness, particularly when there are no better treatment options available. Investigational product (IP) may be temporarily interrupted to allow safety management and will resume the study treatment dose after participant's adverse events are recovered to the Grade 1 level or baseline, per PI's discretion. After the last dose, there will be a safety follow-up period lasting for 1 year and then a long-term follow-up up to 15 years.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must meet all the following inclusion criteria to be enrolled in the study (applied to all patients screened in safety run-in and dose expansion stage, unless specified):
- •Written informed consent must be obtained prior to any procedures that are not considered SOC
- •≥ 18 years old and ≤ 70 years old on the day of signing informed consent, male or female
- •According to the WHO Classification of Tumors of the CNS (2021), definitely diagnosed recurrent or progressive GBM, WHO Grade 4, which must meet all 3 of the following criteria:
- •According to the histological/molecular pathology, diagnosed with GBM WHO grade 4
- •According to the histopathology or radiological imaging, confirmed disease progression or recurrence
- •First recurrence after failure to the SOC therapy of newly diagnosed disease-Stupp regimen (which was surgery + standard RT + concurrent TMZ and adjuvant TMZ), or first recurrence after failure to the SOC therapy of newly diagnosed disease-Stupp regimen (which was surgery + standard RT + concurrent TMZ and adjuvant TMZ) and received Bevacizumab treatment
- •Participants with either unresectable lesions, or with resectable lesions who have undergone prior surgical resection, or with resectable lesions and no planned reoperation within 3 months after enrollment based on Investigator's judgment
- •Participants voluntarily provide the latest archival tumor or fresh biopsies FFPE samples (at least 8 consecutive non-stained sections) for B7H3 expression test by Immunohistochemistry (IHC), and the clinical pathology confirms positive B7H3 expression, defined as the proportion of 2+ and 3+ ≥ 20% (Reference refer to Appendix 13.1) or historical B7H3 positive expression within 12 months at the time of enrollment
- •Karnofsky Performance Status (KPS) score ≥ 60
Exclusion Criteria
- •A patient meeting any of the following criteria is not eligible to participate in this study (applied to all patients screened in safety run-in and dose expansion stages, unless specified):
- •Brainstem and thalamus recurrence, spinal cord dissemination or extracranial metastasis
- •The largest diameter of a single tumor lesion \> 5 cm, or the sum of the largest diameters of multiple lesions \> 6 cm
- •Symptoms and signs of chronic intracranial hypertension that are difficult to control with drugs (such as daily use of Mannitol \> 500 mL or Dexamethasone \> 15 mg or Methylprednisolone \> 80 mg or other hormones at the same dose)
- •Uncontrolled seizure or epilepsy aggravation requiring escalation of antiepileptic therapy over the last 4 weeks
- •Participated in other therapeutic clinical trials within 4 weeks prior to screening
- •Previously received other allogeneic tissue/solid organ transplantation OR other CAR-T cell therapy
- •Previously received Carmustine wafer, oncolytic viruses or other intratumoral implants treatment (e.g., GLIADEL® Wafer)
- •Prior history of severe allergy to any component or biological product of the investigational drug
- •History of other malignancy within 5 years of screening with the following exceptions: a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, c) carcinoma in situ of the breast, d) local prostate cancer after radical resection and/ or definitive RT with stable prostate specific antigen (PSA) levels for 1 year
Arms & Interventions
MT027
Intracerebroventricular administration of MT027 (3×10^7 B7-H3 Targeted UCAR-T-cell)
Intervention: Intracerebroventricular injection of MT027 UCAR-T Cell targeting B7H3 (Biological)
Outcomes
Primary Outcomes
Incidence rate of Dose-limiting toxicity (DLT)
Time Frame: From the first dose to 2 weeks after the second dose
Incidence rate of Dose-limiting toxicity (DLT) after treatment in the safety run-in stage
12-month overall survival (OS) rate
Time Frame: From the first dose to 12 months after the treatment
Secondary Outcomes
No secondary outcomes reported