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, nonsquamous NSCLC (#199)

Bo Gao 1 , Jun Zhao 2 , Jingxun Wu 3 , Lifeng Wang 4 , Meili Sun 5 , Zhiyong Ma 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. The First Affiliated Hospital of Xiamen University, Xiamen, China
  4. Nanjing Drum Tower Hospital, Nanjing, China
  5. Jinan Central Hospital, Jinan, China
  6. The Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, 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 and 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 is a clinical-stage anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages that has shown clinical activity in patients with advanced solid tumors.

Methods: In SAFFRON-103 Cohort H (NCT03666143), patients with PD-L1+, locally advanced/metastatic nonsquamous 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. The primary endpoint was safety/tolerability; other endpoints included investigator-assessed ORR, DCR, PFS, and OS.

Results: Between 07/11/2019 and 23/12/2020, 22 patients were enrolled (median age 60.5 years [range: 41-78]; 68.2% male). Median study follow-up was 11.8 months (range: 0.9-17.9). At the data cut-off (08/11/2021), AEs were reported in 100.0% (any grade) and 59.1% (grade ≥3) of patients. Treatment-related AEs (TRAEs) of any grade or grade ≥3 were observed in 95.5% and 50.0% of patients, respectively; the most common grade ≥3 TRAE was hypertension (13.6%). Serious AEs were reported in 45.5% of patients; two patients experienced TRAEs leading to death (death, n=1; pneumonitis, n=1). Confirmed ORR was 57.1% (95% CI: 34.0, 78.2), with all 12 patients achieving partial response; DCR was 85.7% (95% CI: 63.7, 97.0). Median PFS was 11.1 months (95% CI: 5.5, not estimable [NE]) and median OS was 17.4 months (95% CI: 11.8, NE).

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