Phase 1 Trial of D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma

Within this study, a maximum of 30 patients with recurrent WHO grade III and IV malignant glioma will receive D2C7-IT and 2141-V11 to determine the impact of the combination of D2C7-IT and 2141-V11 on safety. D2C7-IT and 2141-V11 will be delivered sequentially directly into the tumor by Convection Enhanced Delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Based on phase 1 studies of D2C7-IT alone and D2C7-IT in combination with atezolizumab in adult patients with recurrent glioblastoma (GBM), the amount of D2C7-IT to be delivered will be 4613.2 ng/mL (36 mL). 2141-V11 will be dose escalated during the study to determine the maximum tolerated dose (MTD) when used in combination with D2C7-IT. Upon approval of v.9.0 of the protocol, patients will be eligible to receive D2C7-IT + 2141-V11 (via CED and CPL) with or without prior implantation of Tumor Monorail Device (TMD). Patients will be stratified into the following subgroups: * Subgroup #1: Patients accrued before Protocol Version v.5.0 * Subgroup #2: Patients accrued after Protocol Version v.5.0 who did not have a TMD implanted. * Subgroup #3: Patients accrued after Protocol Version v.9.0 for whom a TMD implantation was initiated. Patients who enroll in subgroup #3, once identified as safe to proceed with the TMD (e.g. smaller tumor) and after obtaining their agreement, will receive the TMD approximately 14 days before intracranial D2C7-IT + 2141-V11 infusion in a modified 3+3 design (a minimum of 3 patients and a maximum of 9). All patients who do not meet inclusion criteria for the TMD and/or refuse to receive the TMD, will be treated under subgroup #2 and will proceed directly to CED catheter implantation followed by D2C7-IT + 2141-V11. For patients enrolled subgroup #3, an initial 3 patients will be observed for safety before enrolling the next cohort of 3 patients. Intraoperative CT will be performed post implant to ensure device location accuracy and to check for hemorrhage. Prior to CED catheter insertion for D2C7-IT + 2141-V11 infusion, the first tumor/fluid sampling through the TMD will occur. Repeated tumor/fluid sampling via the TMD will occur before every perilymphatic injection of 2141-V11, i.e., approximately 2 weeks (+ 1 week) after D2C7-IT, which will be repeated again 2 weeks later and then every 3 weeks for 1 year. If fewer than 2 of the first 3 patients who receive the TMD experience an unacceptable adverse event within 14 days of TMD implantation, 3 more patients will receive the TMD. The TMD sampling time can be adjusted from every 3 weeks to every 6 weeks (i.e., every other 2141-V11 infusion) if not enough cellular and genomic material is sampled in the first cohort. With protocol version 10.0, patients who have completed 1 year of CPL subcutaneous injections of 2141-V11 at 2.0 mg every 3 weeks, who benefit from the therapy, and desire to continue on therapy will receive CPL subcutaneous injections of 2141-V11 at 2.0 mg every 4-6 weeks.