SAFFRON-301: Tislelizumab plus sitravatinib in advanced/metastatic NSCLC progressing on/afterchemotherapy and anti–PD-(L)1Authors: Qing Zhou,1 Bo Gao,2 Jie Hu,3 Jun Zhao,4 Mengzhao Wang,5 Kai He,6 Wei Zhang,7 ChunlingLiu,8 Jian Fang,9 Xingya Li,10 Zhehai Wang,11 Marco Matos,12 Vineet Kwatra,13 Xin Li,14 Yaxi Chen,14Juan Zhang,14 Jun Wang,14 Yi-Long Wu15Affiliations: 1Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong
Academy of Medical Sciences), Southern Medical University, Guangzhou, China; 2Blacktown Cancerand Haematology Centre, Blacktown, Australia; 3Fudan University Affiliated Zhongshan Hospital,Shanghai, China; 4Beijing Cancer Hospital, Beijing, China; 5Peking Union Medical Hospital, Beijing,China; 6The Ohio State University College of Medicine, Columbus, OH, USA; 7The First AffiliatedHospital of Nanchang University, Nanchang, China; 8Xinjiang Cancer Hospital, Urumqi, China; 9Beijing
Cancer Hospital, Beijing, China; 10The First Affiliated Hospital of Zhengzhou University, Zhengzhou,China; 11Shandong Cancer Hospital, Jinan, China; 12Pindara Private Hospital, Benowa, Australia;
13Cancer Research South Australia, Adelaide, Australia; 14BeiGene (Beijing) Co., Ltd., Beijing, China;
15
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy ofMedical Sciences), Southern Medical University, Guangzhou, China
ABSTRACTIntroduction: There are limited treatment options for patients with advanced NSCLC who werepreviously treated with chemotherapy and/or anti–programmed cell death protein-1 (PD-1)/–
programmed death-ligand 1 (PD-L1) antibodies. Tislelizumab (TIS) is an anti–PD-1 antibody.
Sitravatinib (sitra) is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor
microenvironment toward an immunostimulatory state. Combining sitravatinib with tislelizumab
may potentially overcome initial checkpoint inhibitor resistance. We present efficacy/safety resultsfrom an open-label, randomized, phase 3 trial evaluating TIS plus sitra versus docetaxel (doc) inpatients with previously treated locally advanced/metastatic NSCLC (NCT04921358).
Methods: Adults (≥18 years) with unresectable locally advanced/metastatic histologically or
cytologically confirmed NSCLC (ECOG PS ≤1), who were previously treated with ≤2 lines of systemic
chemotherapy and anti–PD-(L)1 antibodies were eligible. Patients were randomized (1:1) to TIS 200
mg intravenously once every 3 weeks (Q3W) in combination with sitra 100 mg orally once daily(TIS+sitra) or doc 75 mg/m2 intravenously Q3W. Patients were treated until disease progression,intolerable toxicity, death, or consent withdrawal. Co-primary endpoints were overall survival (OS)and independent-review committee (IRC)-assessed progression-free survival (PFS). Secondaryendpoints included IRC-assessed objective response rate (ORR) by RECIST v1.1 andtreatment-emergent adverse events (TEAEs).
Results: As of Dec 20, 2023, 187 and 190 patients were randomized to TIS+sitra and doc,
respectively (median age [TIS+sitra/doc]: 63.0/63.0 years; median follow-up: 8.0/7.6 months). Most
patients (TIS+sitra/doc) were male (81.8%/79.5%), Asian (93.6%/93.2%), had an ECOG PS 1(74.9%/75.8%), had received 1 line of prior chemotherapy (75.9%/73.7%), and had metastaticdisease (77.0%/74.2%). Median OS (95% confidence interval [CI]) was 11.5 (9.4–14.6) and 11.4 (9.9–15.0) months with TIS+sitra and doc, respectively; hazard ratio (HR) (95% CI), 1.02 (0.75–1.39).
Median IRC-assessed PFS (95% CI) was 4.4 (4.0–5.7) (TIS+sitra) and 2.9 (2.6–4.2) months (doc); HR(95% CI): 0.82 (0.62–1.07). IRC-assessed ORR (95% CI) was 12.3% (8.0%–17.9%) (TIS+sitra) and 12.6%(8.3%–18.2%) (doc). The incidences of TEAEs was higher with TIS+sitra than doc (Table). Grade ≥3TEAEs occurring in ≥5% of TIS+sitra or doc groups were (TIS+sitra/doc): hypertension (13.4%/1.1%),
pneumonia (9.1%/8.5%), palmar-plantar erythrodysesthesia syndrome (6.5%/0%), hypokalemia
WCLC 2024

(5.4%/2.3%), white blood cell count decreased (0%/29.4%), neutrophil count decreased(0.5%/28.8%), neutropenia (0.5%/7.3%), and febrile neutropenia (0%/5.6%). The trial was
terminated due to safety risks/unfavorable benefit-risk analysis.
Conclusions: In patients with previously treated advanced/metastatic NSCLC, TIS+sitra showedsimilar efficacy to doc and was associated with a higher incidence of TEAE.
Table
Patients with treatment-emergent adverse
events, n (%)
Any
Grade ≥3
Serious
Leading to death
Leading to treatment discontinuation (anycomponent)
Any Immune-mediated AEs
Grade ≥3

WCLC 2024

Tislelizumab +sitravatinib(N = 186)

Docetaxel(N = 177)

183 (98.4)
121 (65.1)
83 (44.6)
15 (8.1)
45 (24.2)

162 (91.5)
100 (56.5)
66 (37.3)
5 (2.8)15 (8.5)

91 (48.9)
18 (9.7)

18 (10.2)
4 (2.3)