Sarcoma
Gabriel Tinoco, MD
The Ohio State University
Summary:
Soft-tissue sarcomas encompass a group of rare malignant tumors and account for less than 1% of all adult malignancies in the United States. There are an estimated 13,130 new cases per year and approximately 5,350 deaths. While there are over 100 subtypes, leiomyosarcoma (LMS) is one of the most common subtypes accounting for 10-20% of new soft-tissue sarcoma diagnoses. While surgery can cure localized LMS, 40% of cases still experience local recurrence and/or metastasis. For metastatic disease, beyond first-line therapy, treatment options are scant showing limited effectiveness and the more recently approved agents result in marginal improvements. Median overall survival is about 18 months. Thus, there is an urgent need for novel treatment options. To date immune checkpoint inhibitors (ICIs) have shown minimal activity in LMS but findings indicate that the immunosuppressive factors in the tumor microenvironment of LMS limit their activity. Preclinical studies have shown that all-trans retinoic acid (ATRA), which is used in the treatment of some leukemias, can alter the tumor microenvironment and reduce immune suppressing myeloid-derived suppressors cells (MDSCs). Given that ATRA has been shown to reduce MDSCs within the tumor microenvironment, the investigators propose that this may be an effective strategy to improve immune activation and immunotherapy in a synergistic manner. This phase II study will assess the objective response rate of ATRA in combination with cemiplimab (an ICI) in patients with locally advanced or metastatic LMS. This will be the first study of the combination in LMS or any sarcoma.
Trial Registration: ClinicalTrials.gov Identifier: NCT06528769