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

SAFFRON-301: 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 is to evaluate the efficacy and safety of tislelizumab in combination with sitravatinib compared with docetaxel in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have disease progression following platinum-based chemotherapy and anti-programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) antibody, with the anti-PD-(L)1 antibody administered 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 Contact: Name: BeiGene; Phone Number: 1-877-828-5568; Email: ClinicalTrials@beigene.com

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
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Tweed Heads, New South Wales, Australia, 2485
      • The Tweed Hospital
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Pindara Private Hospital
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research South Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Epping, Victoria, Australia, 3076
      • The Northern Hospital
    • 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 histologicallyor 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: Arm A: Tislelizumab in combination with Sitravatinib; tislelizumab 200 mg intravenously once every 3 weeks in combination with sitravatinib 100 mg orally once a day	Drug: Sitravatinib; administered orally; Drug: Tislelizumab; administered intravenously
Active Comparator: Arm B: Docetaxel; docetaxel 75 mg/m2 intravenously once every 3 weeks	Drug: Docetaxel; administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from randomization to the date of death due to any reason.	From first randomization up to 35 months, approximately
Progression-free survival (PFS) as assessed by Independent Review Committee (IRC)	defined as the time from randomization to the first occurrence of disease progression as determined by the IRC based on RECIST v1.1, or death from any cause, whichever occurs first	From first randomization up to 35 months, approximately

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	defined as the time from randomization to the first occurrence of disease progression as determined by the investigator based on RECIST v1.1, or death from any cause, whichever occurs first	From first randomization up to 35 months, approximately
Overall response rate (ORR)	defined as the proportion of participants with partial response or complete response as determined by the IRC based on RECIST v1.1	From first randomization up to 35 months, approximately
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	From first randomization up to 35 months, approximately
Disease control rate (DCR)	defined as the proportion of participants whose best overall response (BOR) is complete response, partial response or stable disease as determined by the IRC based on RECIST v1.1	From first randomization up to 35 months, approximately
Health-related quality of life (HRQoL) as assessed according to the European Organization and Treatment of Cancer lung cancer module, QLQ-LC13	A score of 1-4 will be administrated for each item in QLQ-LC13. The higher scores will indicate the worse outcomes.	From first randomization up to 35 months, approximately
Health-related quality of life (HRQoL) as assessed according to the European Organization for Research and Treatment of Cancer (EORTC) core cancer (QLQ-C30)	The EORTC QLQ-C30 is completed by the participant. 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) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).	From first randomization up to 35 months, approximately
Health-related quality of life (HRQoL) as assessed according to the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L)	Participant-reported outcomes based on EuroQoL-Five Dimensions, Five Levels (EQ-5D-5L) for all cohorts The EQ-5D- is a generic, self-reported measure of utility that consists of a five-item descriptive system and a visual analogue scale (EQ VAS). The descriptive system has two versions, namely the 3L and 5L, both involving five health dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). In the EQ-5D-5L that will be used, participants may choose from the following five response levels: no problems=1; slight problems=2; moderate problems=3; severe problems=4; and unable to/extreme problems=5. Higher values indicate worst health.	From first randomization up to 35 months, approximately
Number of participants experiencing treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0		From first randomization up to 35 months, approximately
Plasma concentration of sitravatinib		From first randomization up to 35 months, approximately

Collaborators and Investigators

• Sponsor: BeiGene

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): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

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

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