SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer.

Autor:	Zhao J; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China., Yu X; Department of Medical Oncology, Cancer Hospital of University of Chinese Academy of Sciences & Zhejiang Cancer Hospital, Hangzhou, China., Huang D; Department of Thoracic Medical Oncology, Tianjin Cancer Hospital, Tianjin, China., Ma Z; Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, China., Gao B; Blacktown Hospital and University of Sydney, Sydney, New South Wales, Australia., Cui J; Cancer Center, The First Hospital of Jilin University, Changchun, China., Chu Q; Department of Oncology, Tongji Hospital, Wuhan, China., Zhou Q; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China., Sun M; Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, China., Day D; Medical Oncology, Monash Health and Monash University, Melbourne, Victoria, Australia., Wu J; Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China., Pan H; Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China., Wang L; Nanjing Drum Tower Hospital, Nanjing, China., Voskoboynik M; Medical Oncology, Nucleus Network, Melbourne, VIC, Australia and Central Clinical School, Monash University, Melbourne, Victoria, Australia., Wang Z; Department of Internal Medicine - Oncology, Shandong Cancer Hospital & Institute, Jinan, China., Liu Y; Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China., Li H; BeiGene (Shanghai) Co., Ltd, Shanghai, China., Zhang J; BeiGene (Beijing) Co., Ltd, Beijing, China., Peng Y; BeiGene (Shanghai) Co., Ltd, Shanghai, China., Wu YL; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China syylwu@live.cn.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Feb; Vol. 11 (2).
DOI:	10.1136/jitc-2022-006055
Abstrakt:	Background: Some patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) respond poorly to anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) treatments. Combination with other agents may improve the outcomes. This open-label, multicenter, phase 1b trial investigated the combination of sitravatinib, a spectrum-selective tyrosine kinase inhibitor, plus anti-PD-1 antibody tislelizumab. Methods: Patients with locally advanced/metastatic NSCLC were enrolled (Cohorts A, B, F, H, and I; N=22-24 per cohort). Cohorts A and F included patients previously treated with systemic therapy, with anti-PD-(L)1-resistant/refractory non-squamous (cohort A) or squamous (cohort F) disease. Cohort B included patients previously treated with systemic therapy, with anti-PD-(L)1-naïve non-squamous disease. Cohorts H and I included patients without prior systemic therapy for metastatic disease, no prior anti-PD-(L)1/immunotherapy, with PD-L1-positive non-squamous (cohort H) or squamous (cohort I) histology. Patients received sitravatinib 120 mg orally one time per day plus tislelizumab 200 mg intravenously every 3 weeks, until study withdrawal, disease progression, unacceptable toxicity, or death. The primary endpoint was safety/tolerability among all treated patients (N=122). Secondary endpoints included investigator-assessed tumor responses and progression-free survival (PFS). Results: Median follow-up was 10.9 months (range: 0.4-30.6). Treatment-related adverse events (TRAEs) occurred in 98.4% of the patients, with ≥Grade 3 TRAEs in 51.6%. TRAEs led to discontinuation of either drug in 23.0% of the patients. Overall response rate was 8.7% (n/N: 2/23; 95% CI: 1.1% to 28.0%), 18.2% (4/22; 95% CI: 5.2% to 40.3%), 23.8% (5/21; 95% CI: 8.2% to 47.2%), 57.1% (12/21; 95% CI: 34.0% to 78.2%), and 30.4% (7/23; 95% CI: 13.2% to 52.9%) in cohorts A, F, B, H, and I, respectively. Median duration of response was not reached in cohort A and ranged from 6.9 to 17.9 months across other cohorts. Disease control was achieved in 78.3-90.9% of the patients. Median PFS ranged from 4.2 (cohort A) to 11.1 months (cohort H). Conclusions: In patients with locally advanced/metastatic NSCLC, sitravatinib plus tislelizumab was tolerable for most patients, with no new safety signals and overall safety profiles consistent with known profiles of these agents. Objective responses were observed in all cohorts, including in patients naïve to systemic and anti-PD-(L)1 treatments, or with anti-PD-(L)1 resistant/refractory disease. Results support further investigation in selected NSCLC populations. Trial Registration Number: NCT03666143. Competing Interests: Competing interests: QZ reports honoraria for lectures/presentations from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Pfizer, Roche, and Sanofi. DD reports institutional research funding for clinical trials participation from BeiGene, Bristol-Myers Squibb, EpimAb, Harbour BioMed, Maxinovel, MSD, Olema Pharmaceuticals, Pfizer, PhamAbcine, and Roche. MV reports honoraria from MSD and has served as an advisory board member for AstraZeneca. HL, JZhang, and YP are employees of BeiGene. Y-LW reports institutional grants from AstraZeneca, Bristol-Myers Squibb, and Pfizer; and honoraria for lectures/presentations from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Hengrui, MSD, Pfizer, Roche, and Sanofi. All other authors declare no competing interests. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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