Abstract
BACKGROUND
D2C7-IT is a recombinant immunotoxin comprised of a dual-specific antibody fragment targeting EGFRwt and EGFRvIII and a genetically engineered form of the Pseudomonas exotoxin, PE38-KDEL. We report results of a phase 1 trial evaluating D2C7-IT delivered intratumorally by CED.
METHODS
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%. Planned enrollment of two patients per dose level (DL).
RESULTS
As of 5/29/2018, 43 patients have been treated (2 each per DL, but for DLs 3, 6, 9, and 16). Observed dose limiting toxicities include: grade 4 seizure (n=1) on DL3, grade 3 confusion and pyramidal tract syndrome (n=1) on DL13, and grade 4 cerebral edema and grade 3 dysphasia (n=2) on DL17. Grade 2 or higher adverse events possibly related to D2C7-IT include: seizure (grade 4, n=2, grade 3, n=2, grade 2, n=4), cerebral edema (grade 4, n=1), headache (grade 3, n=4; grade 2, n=18), hemiparesis (grade 3, n=4, grade 2, n=10), dysphasia (grade 3, n=2; grade 2, n=9), confusion (grade 3, n=1; grade 2, n=5), thromboembolic event (grade 3, n=2; grade 2, n=1), fatigue (grade 2, n=6), visual field cut (grade 2, n=3), paresthesia (grade 2, n=2), stroke (grade 2, n=2), and hemineglect (grade 2, n=2); one each of grade 3 elevated ALT, urinary tract infection, fall, generalized muscle weakness, encephalopathy, and somnolence; one each of grade 2 elevated AST, papilledema, gait disturbance, intracranial hemorrhage, and urinary incontinence. Fifteen patients are alive. Two patients have partial response and are alive ≥8.2 months and ≥34 months after infusion. CONCLUSION: DL17 is above the maximal tolerated dose. Encouraging efficacy results were observed. After review of efficacy and safety data, DL13 seems the optimal dose, additional patients will be treated on DL13.