ATIM-18. PHASE I DOSE ESCALATION STUDY OF D2C7-IT ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG)
D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin comprising an EGFR-wt and mutant-specific (EGFRvIII) monoclonal antibody and a genetically engineered form of the Pseudomonas exotoxin, PE38-KDEL. The targeting moiety of this immunotoxin binds to EGFRwt and EGFRvIII. We report results of a phase 1 trial evaluating D2C7-IT delivered intratumorally by CED.
Eligible patients are adults with recurrent supratentorial WHO grade III or IV MG; solitary tumor; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS≥70%. There is no limit in number of prior progressions. Two patients are enrolled per dose levels.
As of 6/14/2016, 14 patients have been treated (2 each at dose levels 1, 2, 4, 5 and 6 and 4 at dose level 3). One dose limiting toxicity was observed, a grade 4 seizure (dose level 3). Adverse events possibly related to study include: seizure (grade 4, n=1; grade 1, n=1); headache (grade 3, n=2; grade 2, n=4; grade 1, n=3); elevated ALT (grade 3, n=1; grade 1, n=2); fatigue (grade 2, n=2; grade 1, n=2); visual field cut (grade 2, n=1; grade 1, n=2); elevated AST (grade 2, n=1; grade 1, n=1); cognitive difficulties (grade 2, n=1; grade 1, n=4); stroke (grade 2, n=1; grade 1, n=1); nausea (grade 1, n=3), hemiparesis (grade 1, n=3); one each of grade 2 lymphopenia, generalized muscle weakness, dysphasia, hemineglect, paresthesia, and venous thromboembolic event; and one each of grade 1 anemia, thrombocytopenia, elevated alkaline phosphatase, blurred vision, vomiting, and gait difficulties. Ten patients remain alive with one patient disease-free more than 10 months after infusion.
Infusion of D2C7-IT via CED is safe thus far and encouraging efficacy results are observed. Enrollment is ongoing.
Desjardins, A; Randazzo, D; Chandramohan, V; Sampson, J; Peters, K; Vlahovic, G; Threatt, S; Herndon, J; Boulton, S; Lally-Goss, D; Healy, P; Lipp, E; Friedman, A; Friedman, H; Bigner, D
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