Tislelizumab in Combination With Sitravatinib in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Randomized Phase 3 Study of Tislelizumab in Combination With Sitravatinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer That Progressed on or After Platinum-Based Chemotherapy and Anti-PD-(L)1 Antibody

The purpose of this study was to evaluate the efficacy and safety of tislelizumab in combination with sitravatinib compared to docetaxel in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who experienced disease progression following platinum-based chemotherapy and anti-programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) antibody treatment, with the anti-PD-(L)1 antibody administered either in combination with or sequentially before or after the platinum-based chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Sitravatinib; Drug: Tislelizumab; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Cancer and Haematology Centre
    • Campbelltown, New South Wales, Australia, 2560
      • Campbelltown Hospital
    • Cudgen, New South Wales, Australia, 2487
      • The Tweed Valley Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Pindara Private Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research South Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• China
  • Anhui
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Daping Hospital, Third Military Medical University
    • Chongqing, Chongqing, China, 400037
      • Xinqiao Hospital Affiliated to the Army Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Fuzhou, Fujian, China, 350001
      • Fujian Provincial Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510030
      • Cancer Center of Guangzhou Medical University
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
    • Shenzhen, Guangdong, China, 518116
      • Cancer Hospital Chinse Academy of Medical Sciences, Shenzhen Center
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The Peoples Hospital of Guangxi Zhuang Autonomous Region
    • Nanning, Guangxi, China, 530021
      • The Tumor Hospital Affiliated to Guangxi Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
    • Chenzhou, Hunan, China, 423000
      • The First Peoples Hospital of Chenzhou
    • Hengyang, Hunan, China, 430407
      • The Second Hospital, University of South China
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No Peoples Hospital, the Affiliated Hospital of Nanjing Medical University Branch Cheng
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China, 210009
      • Nanjing First Hospital
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
    • Suzhou, Jiangsu, China, 215000
      • The Second Affiliated Hospital of Soochow University
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • First Affiliated Hospital of Dalian Medical University
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University Branch Laoshan
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital Affiliated to Fudan University
    • Shanghai, Shanghai, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610041
      • Sichuan Cancer Hospital and Institute
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Affiliated Cancer Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Taizhou, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Metastatic or unresectable locally advanced histologically or cytologically confirmed Non-Small Cell Lung Cancer (NCSLC), not amenable to treatment with curative intent
2. Able to provide archival/fresh tumor tissues for biomarker analysis to assess PD-L1 expression and other biomarkers.
3. No known Epidermal Growth Factor Receptor (EGFR) or B-Raf proto-oncogene (BRAF) sensitizing mutation, or anaplastic lymphoma kinase (ALK) rearrangement or ROS proto oncogene 1 (ROS1) rearrangement
4. Radiographic progression per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 on or after anti-PD-(L)1 containing therapy for locally advanced and unresectable or metastatic NSCLC.
5. No prior anticancer therapy having the same mechanism of action as sitravatinib (eg, tyrosine kinase inhibitor with a similar target profile or vascular endothelial growth factor (VEGF)- or VEGFR inhibitor)
6. At least 1 measurable lesion as defined based on RECIST v1.1 by investigator

Key Exclusion Criteria:

1. Has received docetaxel as monotherapy or in combination with other therapies.
2. Squamous NSCLC with central cavitation, or NSCLC with hemoptysis (> 50 mL/day)
3. Participants with tumor shown by imaging to be located around important vascular structures or if the investigator determines that the tumor is likely to invade important blood vessels and may cause fatal bleeding.
4. Active leptomeningeal disease for metastatic NSCLC, or uncontrolled or untreated brain metastasis.
5. Active autoimmune diseases or history of autoimmune diseases that may relapse.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab + Sitravatinib; Participants received 200 mg of intravenous tislelizumab every 3 weeks, combined with 100 mg of oral sitravatinib daily until disease progression, intolerable toxicity, death, or withdrawal of consent, whichever occurred earlier.	Drug: Sitravatinib; 100 mg orally once daily; Other Names: BGB-9468; Drug: Tislelizumab; 200 mg intravenously once every 3 weeks; Other Names: BGB-A317
Active Comparator: Docetaxel; Participants received 75 mg/m² of intravenous docetaxel once every 3 weeks until disease progression, intolerable toxicity, death, or withdrawal of consent, whichever occurred earlier.	Drug: Docetaxel; 75 mg/m^2 intravenously once every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as the time from randomization until the date of death due to any cause. Kaplan-Meier methodology was used to estimate the median OS.	Until the study completion data cut-off date of December 20, 2023, or the last available date confirming participants were alive (a median follow-up of approximately 8 months).
Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)	Defined as the time from randomization until first documentation of disease progression as assessed by the IRC based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occured first. Kaplan-Meier methodology was used to estimate the median PFS.	Until the study completion data cut-off date of December 20, 2023, or the last available date confirming participants were alive (a median follow-up of approximately 8 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) as Assessed by the Investigator	Defined as the time from randomization until first documentation of disease progression as determined by the investigator based on RECIST v1.1, or death from any cause, whichever occured first. Kaplan-Meier methodology was used to estimate the median PFS.	Until the study completion data cut-off date of December 20, 2023, or the last available date confirming participants were alive (a median follow-up of approximately 8 months).
Overall Response Rate (ORR)	Defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as assessed by the IRC per RECIST v1.1.	Until the study completion data cut-off date of December 20, 2023, or the last available date confirming participants were alive (a median follow-up of approximately 8 months).
Duration of Response (DOR)	Defined as the time from the first occurrence of a documented objective response to the time of the first occurrence of disease progression, as determined by the IRC based on RECIST v1.1, or death from any cause, whichever occurs first.	Until the study completion data cut-off date of December 20, 2023, or the last available date confirming participants were alive (a median follow-up of approximately 8 months).
Disease Control Rate (DCR)	Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or stable disease per RECIST v1.1.	Until the study completion data cut-off date of December 20, 2023, or the last available date confirming participants were alive (a median follow-up of approximately 8 months).
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status (GHS) and Physical Functioning Scores	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.	Baseline and Cycle 5 Day 1 (Week 12) and Cycle 7 Day 1 (Week 18)
Change From Baseline in EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Coughing, Dyspnoea, and Chest Pain Scales	The EORTC QLQ-LC13 is the lung cancer module of the QLQ-C30 and measures lung cancer-specific disease and treatment symptoms. It includes 13 questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is "not at all" and 4 is "very much". Raw scores are transformed into a 0 to 100 scale via linear transformation. Lower scores indicate an improvement in symptoms.	Baseline and Cycle 5 Day 1 (Week 12) and Cycle 7 Day 1 (Week 18)
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS)	The EQ-5D-5L comprises a descriptive module that includes five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a Visual Analogue Scale. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS records a participant's self-rated health on a vertical scale from 0 to 100, where 0 is 'the worst health you can imagine and 100 is 'the best health you can imagine'. A higher score indicates better health outcomes.	Baseline and Cycle 5 Day 1 (Week 12) and Cycle 7 Day 1 (Week 18)
Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	From the first dose through 30 days after the final dose or until new anticancer therapy, whichever came first, (a median treatment duration of approximately 4 months in Arm 1 and 2 months in Arm 2).

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• Zhou Q, Zhao J, Gao B, et al. SAFFRON-301: A Phase 3 Study of Tislelizumab With Sitravatinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy and an Anti-PD-1/PD-L1 Antibody. Poster presented at: ESMO Congress 2022; September, 2022; Paris, France.
• Zhou Q, Gao B, et al. SAFFRON-301: Sitravatinib PLUS Tislelizumab in Advanced/Metastatic NSCLC Progressing on/after Chemotherapy and Anti-PD-(L)1.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Tislelizumab
• Other Study ID Numbers: BGB-A317-Sitravatinib-301; 2022-001779-15 (EudraCT Number); SAFFRON-301 (Other Identifier: BeiGene); CTR20211410/CTR20211409 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No