(P 532) MISTOSUS: A PHASE 2 STUDY OF ISCADOR® P IMMUNOTHERAPY FOR PATIENTS WITH RELAPSED OSTEOSARCOMA AND RESECTED PULMONARY METASTASES

Objective: The prognosis of pediatric and adolescent/young adult (AYA) patients with relapsed osteosarcoma (OS) is poor, despite complete surgical resection of metastatic disease. Historical studies cite a 12-month event-free survival of 20-35%. Preventing future recurrence of osteosarcoma (OS) in these patients is pivotal to improving survival outcomes. IscadorP (Iscador AG, Arlesheim, Switzerland), is a fermented aqueous extract from naturally derived components of the mistletoe plant (Viscum album L.) grown on pine trees (IscadorP = Pini). In addition to direct cytotoxicity, IscadorP stimulates an immunologic response against tumor cells through interactions with neutrophils, natural killer cells and T-lymphocytes. It is widely used as complementary cancer therapy in Europe. A small study by Longhi et. al. (2014) randomized patients with surgically resected OS metastases to either IscadorP or oral etoposide and showed a 12-month post relapse event free survival (PREFS-12) of 55.5% in the IscadorP group compared to 27.3% in the etoposide group, which persisted at 84-months. The present study, MISTOSUS (NCT05726383), is an open-label, single-arm, phase 2 clinical trial evaluating the efficacy of IscadorP in pediatric/AYA patients with pulmonary relapse of OS. The primary endpoint is PREFS-12 compared to a historical control of 30%. Secondary endpoints include time to relapse and quality of life. Exploratory objectives include correlative studies to evaluate histologic and immunologic response to IscadorP therapy.

Methods: Eligible patients are 8-30 years of age, with at least one episode of OS relapse in the lung. Participants must be within 8 weeks of surgical resection of all gross metastatic disease and have histologic confirmation of relapse. Patients are ineligible if they do not meet organ function requirements, are pregnant, breastfeeding, have another active malignancy, CNS metastases, or have concurrent inflammatory diseases which would confound the results of the study. IscadorP is administered subcutaneously three times weekly (Mon, Wed, Fri) for 13, 4-week cycles. Dosing begins at the lowest dose level and is then titrated up if tolerated and to achieve optimal immune response based on local skin reaction. All patients begin with Series 0 (0.01, 0.01, 0.1, 0.1, 1, 1, 1mg) for minimum of 14 doses, followed by Series 1 (0.1, 0.1, 1, 1, 10, 10, 10mg) for minimum of 14 doses, and then Series 2 (1, 1, 10, 10, 20, 20, 20mg), which is continued through week 52 (total 13 cycles). Patients are removed from study for disease progression or unacceptable toxicity. Target enrollment is 26 patients. PREFS-12 and time to relapse are evaluated based on clinical exams and imaging. Quality of life is assessed with age-based NIH PROMIS® measures. Blood samples from all enrolled patients are analyzed by flow cytometry using T-cell and myeloid functional panels as well as CodePlex Secretome to collect cytokine data. When available, histology of pulmonary tumor specimens occurring after treatment with IscadorP are compared with pre-treatment biopsy/surgery specimens or archival tissue. Flow cytometry and immunofluorescence using multiplex IF Vectra T-cell and myeloid functional panels are also performed on these tumor specimens and compared with baseline archived tissue.

Results: None yet available

Conclusion: An Investigational New Drug application has been obtained through the United States Food and Drug Administration (159616). Institutional Review Board approval has been obtained at Hackensack Meridian Health. This multi-institutional clinical trial will begin enrolling patients in August 2023 at Hackensack Meridian Health in Hackensack, NJ, and MD Anderson Cancer Center in Houston, TX. Clinical trial information: NCT05726383. Results from this study will evaluate the efficacy of IscadorP to improve survival in relapsed lung OS.

Funding Acknowledgement: Study funded in part by generous grants from Golfers Against CancerTM and the Susan Zabransky Hughes Memorial Run.