Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Safety and efficacy of sitravatinib + tislelizumab in patients with PD-L1+, locally advanced/metastatic, squamous NSCLC (#200)

Bo Gao 1 , Jun Zhao 2 , Dingzhi Huang 3 , Meili Sun 4 , Zhiyong Ma 5 , Qian Chu 6 , Yunpeng Liu 7 , Zhehai Wang 8 , Xin Li 9 , Hui Li 10 , Juan Zhang 9 , Jingchao Sun 9 , Yanyan Peng 10 , Yi-Long Wu 11 , Paul Smart 12
  1. Blacktown Cancer and Haematology Centre, Blacktown, NSW, Australia
  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China
  3. Tianjin Cancer Hospital, Tianji, China
  4. Jinan Central Hospital, Jinan, China
  5. The Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, China
  6. Tongji Hospital, Wuhan, China
  7. The First Hospital of China Medical University, Shenyang, China
  8. Shandong Cancer Hospital & Institute, Jinan, China
  9. BeiGene (Beijing) Co., Ltd., Beijing, China
  10. BeiGene (Shanghai) Co., Ltd., Shanghai, China
  11. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
  12. Beigene, Warriewood, NSW, Australia

Aims: Sitravatinib, an investigational selective tyrosine kinase inhibitor, reduces the number of myeloid-derived suppressor cells, which promotes expansion of antitumor cytotoxic T cells and increases the ratio of M1/M2-polarized macrophages. Tislelizumab, a clinical-stage anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages, has shown clinical activity in patients with advanced solid tumors.

Methods: In SAFFRON-103 Cohort I (NCT03666143), patients with PD-L1+, locally advanced/metastatic squamous NSCLC without prior systemic treatment in the metastatic setting were enrolled; PD-L1+ was defined as PD-L1 staining on ≥1% of tumor cells (VENTANA SP263 immunohistochemistry assay). Patients with documented EGFR mutation, ALK/ROS1 rearrangement, or BRAF mutation were not eligible. Patients received sitravatinib 120mg orally QD plus tislelizumab 200mg intravenously Q3W until unacceptable toxicity, withdrawal, or death. Primary endpoint was safety/tolerability; other endpoints included investigator-assessed ORR, DCR, PFS, and OS.

Results: Between 12/05/2020 and 10/02/2021, 24 patients were enrolled (median age 65.0 years [range: 56-71]; 91.7% male). Median study follow-up was 9.4 months (range: 0.4-16.2). At the data cut-off (08/11/2021), AEs were reported in 100% (any grade) and 66.7% (grade ≥3) of patients. Treatment-related AEs (TRAEs) of any grade or grade ≥3 were observed in 95.8% and 58.3% of patients, respectively; hypertension was the most common grade ≥3 TRAE (16.7%). Serious AEs were observed in 50.0% of patients; AEs led to death in two patients (death, n=1; pneumonia, n=1), neither AE was considered treatment related. Confirmed ORR was 30.4% (95% CI: 13.2, 52.9), with all seven patients achieving partial response; DCR was 78.3% (95% CI: 56.3, 92.5). Median PFS was 5.4 months (95% CI: 2.8, 8.6), while median OS was not reached (95% CI: 6.7, not estimable).

Conclusions: Sitravatinib plus tislelizumab demonstrated a manageable safety/tolerability profile and antitumor activity in systemic therapy-naïve patients with PD-L1+, locally advanced/metastatic squamous NSCLC.

  1. Acknowledgments: This study was sponsored by BeiGene, Ltd. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Tamsin Grewal, MSc and Louise Oakes, PhD, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd. Editorial support was provided by Elizabeth Hermans, PhD, of BeiGene, Ltd.