B7H3-Directed Intraperitoneal Radioimmunotherapy With Radioiodinated Omburtamab for Desmoplastic Small Round Cell Tumor and Other Peritoneal Tumors: Results of a Phase I Study

PURPOSE Desmoplastic small round cell tumor (DSRCT), a rare sarcoma of adolescents/young adults primarily involving the peritoneum, has a long-term survival of < 20% despite aggressive multimodality treatment. B7H3 is expressed on DSRCT cell surface, providing a target for antibody-based immunotherapy. PATIENTS AND METHODS In this phase I study, we evaluated the safety, pharmacokinetics, and biodistribution of intraperitoneal (IP) radioimmunotherapy (RIT) with the anti-B7H3 murine monoclonal antibody 1311-omburtamab in patients with DSRCT or other B7H3-expressing tumors involving the peritoneum. After thyroid blockade, patients received I-131-omburtamab as a single IP injection at escalated activities from 1.11 to 3.33/GBq/m(2). A prior tracer dose of IP 74 MBq I-12(4)-omburtamab was used for radioimmuno-positron emission tomography imaging. Each injection was followed by IP saline infusion. RESULTS Fifty-two patients (48, three, and one with DSRCT, peritoneal rhabdomyosarcoma, and Ewing sarcoma, respectively) received IP I-131-omburtamab administered on an outpatient basis. Maximum tolerated dose was not reached; there were no dose-limiting toxicities. Major related adverse events were transient: grade 4 neutropenia (n = 2 patients) and thrombocytopenia (n = 1), and grade 1 (10%) and grade 2 (52%) pain lasting < 2 hours related to saline infusion. Hypothyroidism was not observed, and antidrug antibody was elicited in 5%. Mean (+/- SD) projected peritoneal residence time was 22.4 +/- 7.9 hours. Mean projected absorbed doses for 13I-omburtamab based on I-124-omburtamab dosimetry to normal organs were low and well within tolerable limits. More than 80% I-131 remained protein bound in blood 66 hours after RIT. On the basis of peritoneal dose and feasibility for outpatient administration, the recommended phase II activity was established at 2.96 GBq/m(2). Patients with DSRCT receiving standard whole-abdominal radiotherapy after RIT did not experience unexpected toxicity. CONCLUSION IP RIT I-131-omburtamab was well tolerated with minimal toxicities. Radiation exposure to normal organs was low, making combination therapy with other anticancer therapies feasible. (C) 2020 by American Society of Clinical Oncology