The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer.

Abstract

1070 Background: Anti-PD-1 antibody plus chemotherapy has been demonstrated promising anti-tumor activity in patients with locally recurrent or metastatic triple negative breast cancer (TNBC). However, this regime only limited to TNBC patients with PD-L1 positive. As antiangiogenic agents could enhance the response to immune checkpoint inhibitors, we conducted this phase 2 study to assess the efficacy and safety of novel chemotherapy-free regimen of sitravatinib (targets receptor TKI against TYRO3, AXL, MERTK and VEGF family of receptors) in combination with tislelizumab (anti-PD-1 antibody) in patients with locally recurrent or metastatic TNBC regardless of PD-L1 status. Methods: Patients with locally recurrent or metastatic TNBC were included and divided into two cohorts. Patients received 70 mg (cohort A) or 100 mg (cohort B) sitravatinib QD PO and 200 mg tislelizumab IV Q3W until disease progression or intolerable toxicity. The primary endpoints included overall response rate (ORR) (cohort A and B) and rate of grade ≥3 treatment-related adverse events (AEs) (cohort B). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), 1-year overall survival rate and safety/tolerability. In cohort A, the first statistical analysis would be performed when 12 patients were enrolled; if ≥1 of 12 patients were with confirmed response during the first stage, additional 9 patients would be enrolled to the second stage based on Simon's two-stage design. We would deem cohort A to be statistically superior to a historical control of 8% under the settings if > 3 of 21 patients responded (one-sided a = 0.1 and power of 80%). Patients’ recruitment in cohort B would begin after completing the recruitment in cohort A. Results: Herein we reported the preliminary results in cohort A. Four patients were with confirmed response during the first stage, and additional nine patients were enrolled to the second stage. A total of 21 patients with 0-3 lines of prior chemotherapy were included from April 2021 to September 2021. The median age was 51 (32-66) years and 20 (95%) patients had ECOG PS 0. At data cut off 13 Jan 2022, 19 patients were alive, 11 are still on treatment. The confirmed ORR was 38.1% (95% CI, 18.1%-61.6%) based on current 21 efficacy evaluable patients. DCR was 95.2% (95% CI, 76.2%-99.9%), and median PFS was 7.0 (95% CI, 3.7 - not reached) months. 4/21 (19%) of patients experienced grade 3 treatment-related AEs. Grade 3 AEs reported in ≥5% of patients were aspartate aminotransferase increased (9.5%) and palmar-plantar erythrodysaesthesia syndrome (9.5%). No patients experienced grade 4 AEs. Conclusions: Sitravatinib combined with tislelizumab demonstrated clinically meaningful anti-tumor activity and had a manageable safety profile. Clinical trial information: NCT04734262.