M032 Oncolytic Virus + Pembrolizumab

Starting at week four, patients will undergo treatment on the same day, and every three weeks thereafter, with intravenous infusion of 200mg of Pembrolizumab . A total of 3 combined doses of Pembrolizumab and M032 will be given.

Phase I/Cohort I: For the Phase I portion of this trial, patients whose malignant gliomas recur after undergoing initial surgical resection, standard of care radiotherapy (60Gy) and standard of care temozolomide chemotherapy and who are candidates for, and would bene-fit from, a surgical debulking.

Patients whose tumors have unmethylated MGMT promoters who have completed radiation therapy will also be eligible, regardless of whether or not they received temozolomide, since some centers are not using temozolomide in these patients. M032 will initially be administered directly into the tumor bed at the time of craniotomy and immediately after resection of the tumor.

This Phase I (Cohort I and Cohort II) and Phase II trial is designed to confirm the safety and tolerability of Pembrolizumab when given in conjunction with M032, an Oncolytic Herpes Simplex Virus (oHSV) that expresses IL-12 and perform the Phase II portion using a Recommended Phase 2 Dose (RP2D) of M032 (provided by the Phase I) when given in conjunction with Pembrolizumab for recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or glio-sarcoma).

Registro actualizado en ClinicalTrials.gov →

• Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, and is deemed a potential candidate for resection of the recurrent tumor.
• Prior therapy: Patients must have failed external beam radio-therapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment.
• Patient must have MRI findings consistent with probable malignant glioma, have no previous diagnosis of glioma, and have had either no history of any surgery for brain tumor. The exception to this requirement is that patients who have under-gone biopsy for diagnosis only and have not received any other treatment. All patients must be potential candidates for resection of the probably malignant glioma tumor.
• Should a patient in Phase I/Cohort II or Phase II be found on final pathologic diagnosis to not have a glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, he/she will receive no other doses of M032 other than that administered at the time of craniotomy, nor will he/she receive any doses of Pembrolizumab. He/she will be followed for evidence of toxicity of M032 only and will be considered off-study for all efficacy and other secondary endpoints.

Criterios de inclusión tal como figuran en el registro, recortados. La lista completa, con las exclusiones, está en el registro actualizado.