Abstract CT006: Intraperitoneal radioimmunotherapy for desmoplastic small round cell tumor: Results of a phase I study (NCT01099644)
Authors: Modak Shakeel , Carrasquillo Jorge , LaQuaglia Michael , Pat Zanzonico , Heaton Todd , Cheung Nai-Kong , Pandit-Taskar Neeta 
Published: August 2018

Abstract
Background / Objectives: Desmoplastic small round cell tumor (DSRCT), a rare sarcoma of adolescents and young adults, has a long-term survival of &lt;20% despite aggressive multimodality therapy, warranting a search for novel treatments. The murine monoclonal IgG1 antibody 8H9 recognizes cell surface antigen 4Ig-B7H3 and binds to 96% of DSRCTs with restricted normal tissue reactivity. DSRCT recurrences often present as multifocal peritoneal implants. We hypothesized that intraperitoneal (IP) radioimmunotherapy (RIT) by virtue of prolonged residence time and slow transfer to the circulation, may selectively target IP DSRCT.
Design / Methods: We conducted a phase I study of radioiodinated 8H9 to evaluate toxicity, pharmacokinetics, biodistribution and efficacy. Cohorts of 3-6 patients were treated with escalated doses of IP 131I-8H9. A prior dose of 2mCi 124I-8H9 IP was used to acquire PET images and biodistribution data. Toxicity was monitored clinically and biochemically. Pharmacokinetics was studied using serial blood draws.
Results: Forty-one DSRCT patients were treated at doses of 30-90mCi/m2. Maximum tolerated dose was not reached; there were no dose-limiting toxicities. Major adverse events (n=1 each) were transient: grade 3 transaminitis, neutropenia, and thrombocytopenia. Blood and peritoneal half-times were 32.5h and 14.6h respectively. Mean projected absorbed doses to blood, kidney, liver, lung and spleen were 0.7,1.72,1.92,0.64 and 1.03 rad/mCi 131I-8H9 respectively (n=12 patients analyzed). Dehalogenation was insignificant: &gt;80% blood 131I remained protein-bound 66h post-RIT. Recommended phase II dose was 80mCi/m2. External beam intensity-modulated whole-abdominopelvic radiotherapy (WAP-IMRT) to 3000cGy was administered after protocol therapy to 25 patients without unexpected adverse events. Median progression-free survival (PFS) from RIT for first remission patients (n=21) undergoing gross total resection followed by RIT and whole-abdominal radiotherapy was 17.9±1.7 months. Of these, 19 and 13 patients are PF and overall survivors respectively at a median of 13 months post-RIT. In contrast patients with gross residual disease pre-RIT or those receiving RIT in ≥2nd remission (n=20) had median PFS of 8.1±3.5 months (p&lt;0.05 for PFS and OS).
Conclusions: 124I-8H9-directed radioimmuno-PET successfully determined biodistribution, whole-body and organ exposure. 131I-8H9 IP RIT had a satisfactory safety profile and appears to have activity against micro-metastatic DSRCT. A phase II trial combining IP RIT and WAP-IMRT will commence shortly.
Citation Format: Shakeel Modak, Jorge Carrasquillo, Michael LaQuaglia, Zanzonico Pat, Todd Heaton, Nai-Kong Cheung, Neeta Pandit-Taskar. Intraperitoneal radioimmunotherapy for desmoplastic small round cell tumor: Results of a phase I study (NCT01099644) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT006.