CTIM-23. DOSE ESCALATION TRIAL OF FC-ENGINEERED ANTI-CD40 MONOCLONAL ANTIBODY (2141-V11) ADMINISTERED INTRATUMORALLY WITH D2C7-IT VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMAS (RMGS)

Abstract BACKGROUND D2C7-IT, a novel immunotoxin-based cytotoxic therapy, targets epidermal growth factor receptor (EGFR) and mutant EGFR variant III. In preclinical studies, D2C7-IT kills tumor cells prolongs survival, but is unable to generate cures in all animals. We hypothesized that immunosuppression glioblastoma limits efficacy. Eliminating via CD40 co-stimulation anticipated enhance D2C7-IT-induced antitumor responses. murine glioma models, CED of D2C7-IT+αCD40 generated long-term tumor-specific adaptive immunity. Hence, we are conducting phase 1 trial D2C7-IT+2141-V11 (αhuman-CD40) administered rMG patients. METHODS Eligibility includes adult patients with solitary supratentorial (WHO grade 3/4); ≥ 4 weeks after chemotherapy, bevacizumab, or study drug; adequate organ function; KPS 70%. Cohorts 3 treated increasing doses 2141-V11 determine the maximum tolerated dose when sequentially following (166,075 ng) at 0.5 mL/hr. Five levels (DLs) evaluated (2141-V11 at: #1: 0.70 mg; #2: 2.0 #2**: 3.0 mg #2*: 4.0 #3: 7.0 mg). RESULTS As May 29, 2022, 13 were (3 on DL1, DL2, DL2**; 2 DL3 DL2*). No dose-limiting toxicities observed; however, lower DLs added due higher frequency adverse events (AEs) expected DL2* (fever, neurologic symptoms). All remain alive 0.7-10.6 months therapy. Grade AEs include: headache (grade 3, n = 1; 2, 4); pyramidal tract disorder 2); paresthesia 1); dysphasia seizures 2; fever one each depressed level consciousness, fatigue, concentration impairment. Enrollment ongoing. CONCLUSIONS Intratumoral administration safe, encouraging efficacy results observed.