Synapse - B7H3-directed intraperitoneal radioimmunotherapy with radioiodinated omburtamab for desmoplastic small round cell tumor and other peritoneal tumors: Results of a phase I study

B7H3-directed intraperitoneal radioimmunotherapy with radioiodinated omburtamab for desmoplastic small round cell tumor and other peritoneal tumors: Results of a phase I study Journal Article

Authors:	Modak, S.; Zanzonico, P.; Grkovski, M.; Slotkin, E. K.; Carrasquillo, J. A.; Lyashchenko, S. K.; Lewis, J. S.; Cheung, I. Y.; Heaton, T.; LaQuaglia, M. P.; Cheung, N. K. V.; Pandit-Taskar, N.
Article Title:	B7H3-directed intraperitoneal radioimmunotherapy with radioiodinated omburtamab for desmoplastic small round cell tumor and other peritoneal tumors: Results of a phase I study
Abstract:	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 131I-omburtamab in patients with DSRCT or other B7H3-expressing tumors involving the peritoneum. After thyroid blockade, patients received 131I-omburtamab as a single IP injection at escalated activities from 1.11 to 3.33/GBq/m2. A prior tracer dose of IP 74 MBq124I-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 131I-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 5 2 patients) and thrombocytopenia (n 5 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 (6 SD) projected peritoneal residence time was 22.4 6 7.9 hours. Mean projected absorbed doses for 131I-omburtamab based on 124I-omburtamab dosimetry to normal organs were low and well within tolerable limits. More than 80% 131I 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/m2. Patients with DSRCT receiving standard whole-abdominal radiotherapy after RIT did not experience unexpected toxicity. CONCLUSION IP RIT 131I-omburtamab was well tolerated with minimal toxicities. Radiation exposure to normal organs was low, making combination therapy with other anticancer therapies feasible. Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
Keywords:	adult; cancer chemotherapy; cancer survival; clinical article; young adult; unclassified drug; fatigue; neutropenia; drug safety; positron emission tomography; follow up; cytoreductive surgery; pain; phase 2 clinical trial; bone marrow suppression; thrombocytopenia; protein; radiation exposure; ewing sarcoma; minimal residual disease; dosimetry; radioactivity; radiopharmaceutical agent; single drug dose; phase 1 clinical trial; hypothyroidism; rhabdomyosarcoma; radiation safety; radioimmunotherapy; disease exacerbation; liothyronine; peritoneum tumor; allotransplantation; thrombocyte transfusion; desmoplastic small round cell tumor; filgrastim; potassium iodide; radioiodination; plasma clearance; human; male; female; priority journal; article; omburtamab i 124; b7h3 protein; omburtamab i 131
Journal Title:	Journal of Clinical Oncology
Volume:	38
Issue:	36
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2020-12-20
Start Page:	4283
End Page:	4291
Language:	English
DOI:	10.1200/jco.20.01974
PUBMED:	33119478
PROVIDER:	scopus
PMCID:	PMC7768336
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098471074&doi=10.1200%2fJCO.20.01974&partnerID=40&md5=9932a480e7aad82c6a54f7e62d1b8099
Notes:	Article -- Export Date: 1 February 2021 -- Source: Scopus