Ensayos clínicos

Inclusion Criteria:

• Histologically confirmed diagnosis of medulloblastoma.
• SHH, Group 3, or Group 4 according to World Health Organization 2016 classification.
• Recurrent or refractory to frontline therapy, defined as:
  • For Part 1 only: Recurrent (maximum of 2 recurrences) or refractory to frontline therapy. Prior frontline or second-line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens.
  • For Part 2 only: Recurrent (maximum of 1 recurrence) or refractory to frontline therapy. Patients with recurrent disease must have received second-line chemotherapy for progressive disease. Prior frontline or second-line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens.
• Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously.
• Performance status score of 50 to 100, both inclusive, on the Lansky [<16 years] or Karnofsky [≥16 years] scales.
• Aged 3 to 19 years, both inclusive, at the time of the first planned dose of trial treatment.
• Life expectancy of at least 3 months, as judged by the Investigator.
• Acceptable hematological status and liver and kidney function.

Exclusion Criteria:

• Obstructive or symptomatic communicating hydrocephalus as determined by Ommaya patency/cerebrospinal fluid (CSF) flow study.
• Any tumor lesion measuring >15 mm in the smallest diameter
• Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts.
• Grade 4 nervous system disorder. Stable neurological deficits due to brain tumor or surgery and hearing loss are allowed.
• Uncontrolled life-threatening infection.
• Received radiation therapy (focal or cranio-spinal irradiation), systemic or intrathecal cytotoxic chemotherapy, or intrathecal immunotherapy (corticosteroids not included) less than 3 weeks prior to the Screening Visit. Received nitrosoureas less than 6 weeks or monoclonal antibodies less than 5 half-lives prior to the Screening Visit.
• Received systemic or intrathecal cytotoxic chemotherapy or intrathecal immunotherapy (corticosteroids not included) less than 3 weeks prior to the screening visit.
• Received any prior anti-B7-H3 treatment.
• Non-hematologic organ toxicity Grade 3 or above; specifically, any renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity.
• Females of childbearing potential, who are pregnant, breast feeding, intend to become pregnant, or are not using highly effective contraceptive methods or males who are not using highly effective contraceptive methods.