Open-label, Dose Confirmation Study of Interstitial 131I-Chtnt-1/b Mab for the Treatment of Glioblastoma Multiforme (GBM) at First Relapse: Interim Results.

2035 Background: GBM is the most common and clinically aggressive primary brain tumor. For recurrent GBM, treatment by surgical resection, radiation therapy, and chemotherapy remains palliative, and prolonged survival has not been convincingly demonstrated with any treatment strategy. 131I-chTNT-1/B MAb (Cotara) is a radioiodinated chimeric monoclonal antibody specific for DNA and histone H1 complex exposed in necrotic core of malignant gliomas. Prior studies suggested improved survival with interstitial 131I-chTNT-1/B MAb in recurrent GBM patients. Methods: Phase II, open-label, dose confirmatory study of patients aged 18 to 75 yrs with histologically confirmed GBM at first relapse, a clinical target volume (CTV) of 5 to 60 cc, and KPS ≥70%. 131I-chTNT-1/B MAb was administered by convection enhanced delivery via 2 catheters placed under stereotactic guidance, at 0.18 mL/h for approximately 25 hours at a dose of 2.5 mCi/cc of CTV. Forty patients were planned to assess safety and tolerability. Additional endpoints included overall survival (OS), progression free survival (PFS), and proportion of patients alive at 6 months. Results: Forty-one patients (26 males) were enrolled and received study drug. Median age was 52 years (24-74). Median CTV was 28.3 cc (1.6-65.8) and median KPS was 80 (70-100). The median administered therapeutic dose was 66.9 mCi (3.5-148) with most patients receiving >90%; one received only 3% due to an infusion pump malfunction. The most common overall adverse events (AEs) (> 10%) were: brain edema (32%), headache (22%), convulsions (20%) and amnesia (12%). The most common drug-related AEs were brain edema (27%) and convulsions (15%) and most were managed with corticosteroids. Grade 3-4 drug-related AEs (all neurologic) were reported in 22% of patients. Interim median OS is currently at 38 weeks and median PFS at 23 weeks. Conclusions: Single interstitial administration of 131I-chTNT-1/B MAb at 2.5 mCi/cc was generally tolerated in this study of patients with recurrent GBM. Though follow-up is continuing, the current median survival of 38 weeks is encouraging and further clinical development is warranted.