Phase Ib trial of C019199, an oral TME modulator targeting CSF-1R/DDRs/VEGFR2, in relapsed or refractory osteosarcoma.

Abstract

11510 Background: C019199 is an oral drug candidate that modulates the tumor micro-environment (TME) through targeting CSF-1R/DDRs/VEGFR2. Previous phase Ia study of C019199 as a mono-therapy for advanced solid tumors has shown promising safety and anti-tumor activity. The osteosarcoma cohort of this Phase Ib study aims to further evaluate the safety and efficacy of C019199 in patients with relapsed or refractory osteosarcoma who had failed in the first-line chemotherapy. Methods: In this study, patients of ≥16 years and <76 years with histologically or cytologically confirmed osteosarcoma, progressing after at least one prior chemotherapy, were enrolled. The dosing regimen of C019199 is 200 mg once daily, with continuous administration over 21-day treatment cycles. Imaging assessments are performed every two cycles. The treatment continues until disease progression, intolerable toxicity, or withdrawal of informed consent by the patient. The primary endpoint is the incidence of adverse events (AEs) and serious adverse events (SAEs). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 30 patients with relapsed or refractory osteosarcoma were enrolled from October 2023 to November 2024. Median age was 29 years (range, 16–62), with 60% males. The most common treatment-related adverse events (TRAEs) were leukopenia (60%), increased creatine phosphokinase (53.3%), increased lactate dehydrogenase (53.3%), neutropenia (53.3%), thrombocytopenia (46.7%), diarrhea (43.3%), increased aspartate aminotransferase (43.3%), and lymphopenia (40.0%). Grade 3 or higher TRAEs were observed in merely 7 patients (23.3%) including neutropenia (3 pts), lymphopenia (2 pts), thrombocytopenia (1 pts), hypertension (1 pts), syncope (1 pts), and dyspnea (1 pts). One patient achieved a partial response (an ORR of 3.3%), while majority of patients achieved stable conditions with a DCR of 73.3%. Median PFS was 181 days, and the 3-month PFS rate was 66.7%. Conclusions: The data has demonstrated that C019199 exhibited a promising anti-tumor activity in patients of relapsed or refractory osteosarcoma. Combined with the encouraging tolerability and safety data, it suggests that C019199 has the potential to effectively benefit survival and improve quality of life for patients of this indication. The Phase Ib study is concluding, and a Phase III study is planned. Clinical trial information: CTR20202045 .