A phase II study of C019199 in combination with sintilimab in patients with locally recurrent or metastatic triple negative breast cancer (TNBC).

e13134 Background: C019199 is an oral drug candidate that modulates the tumor micro-environment (TME) through targeting CSF-1R/DDRs/VEGFR2. Previous phase I study of the combination of C019199 and Sintilimab (PD-1 monoclonal antibody) for treatment of advanced solid tumors has shown promising safety and anti-tumor activity. This phase II study is to evaluate the safety and efficacy of the combination of C019199 and Sintilimab in patients (pts) with locally recurrent or metastatic TNBC who had received at least one line of standard systemic therapy. Methods: An open label, multi-center phase II study of C019199 combined with Sintilimab is currently enrolling. Eligible subjects (age of ≥18 years and < 76 years) with histologically or cytologically confirmed locally recurrent or metastatic TNBC who had received at least one line of standard systemic therapy were enrolled. C019199 was dosed at 200 mg orally QD with Sintilimab dosed at 200 mg IV Q3W. Treatment continues until progression, unacceptable toxicity, or withdrawal of informed consent by the patients. The primary endpoints are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), disease control rate (DCR), and overall survival (OS). Results: Starting from April 15, 2024 till January 5, 2025, a total of 17 pts with TNBC were enrolled in the study, with 14 of them having at least one treatment response assessment . The median age was 54 years (range, 32-70 years); of whom 12 pts (71%) received two or more prior lines of systemic therapies, 5 pts (29%) received PD-1/PD-L1 antibody and 3 pts (18%) received ADC therapy previously. The median follow-up time was 2.4 months. Target lesion shrinkage was observed in 12 out of 14 pts, with one target lesion unchanged and another one enlarged. 2 pts achieved partial response (one has maintained partial response for more than 9 months till now and the other for 5 months)， and 10 pts achieved stable conditions (SD), resulting in an ORR of 14% and DCR of 86%. Median PFS and median OS have not been achieved. The most frequent (≥10%) grade ≥3 treatment-related adverse events (TRAEs) were neutropenia (17.6%), thrombocytopenia (11.8%) and elevated aspartate aminotransferase (11. 8%). The trial has been well underway and pursued actively. Conclusions: The combination of C019199 and Sintilimab has shown promising anti-tumor activity in pts of locally recurrent or metastatic triple-negative breast cancer. The most majority of pts had experienced tumor shrinkage in target lesions from baseline. Also a good overall safety and tolerability in pts were observed. The phase II study is ongoing to accumulate more clinical data. Clinical trial information: NCT06220318 .