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

Non-Small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04921358
• Other study ID #: BGB-A317-Sitravatinib-301
• Secondary ID: 2022-001779-15SA
• Status: Terminated
• Phase: Phase 3
• Start date: July 27, 2021
• Est. completion date: December 20, 2023

Study information

• Verified date: February 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 377
• Est. completion date: December 20, 2023
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Tislelizumab
administered intravenously
• Docetaxel
administered intravenously
• Sitravatinib
administered orally

Locations

Country	Name	City	State
Australia	Cancer Research South Australia	Adelaide	South Australia
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Blacktown Cancer and Haematology Centre	Blacktown	New South Wales
Australia	Cairns Hospital	Cairns	Queensland
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Australia	Monash Health	Clayton	Victoria
Australia	The Northern Hospital	Epping	Victoria
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	Sunshine Hospital	St Albans	Victoria
Australia	The Tweed Hospital	Tweed Heads	New South Wales
China	Beijing Cancer Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Changzhou No Peoples Hospital, the Affiliated Hospital of Nanjing Medical University Branch Cheng	Changzhou	Jiangsu
China	Sichuan Cancer Hospital and Institute	Chengdu	Sichuan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The First Peoples Hospital of Chenzhou	Chenzhou	Hunan
China	Daping Hospital, Third Military Medical University	Chongqing	Chongqing
China	Xinqiao Hospital Affiliated to the Army Medical University	Chongqing	Chongqing
China	First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	Guangdong Provincial Peoples Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital	Hefei	Anhui
China	The Second Hospital, University of South China	Hengyang	Hunan
China	Jinan Central Hospital	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	The Peoples Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	The Tumor Hospital Affiliated to Guangxi Medical University	Nanning	Guangxi
China	The Affiliated Hospital of Qingdao University Branch Laoshan	Qingdao	Shandong
China	Affiliated Zhongshan Hospital of Fudan University	Shanghai	Shanghai
China	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Rui Jin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong
China	Liaoning Cancer Hospital and Institute	Shenyang	Liaoning
China	Cancer Hospital Chinse Academy of Medical Sciences, Shenzhen Center	Shenzhen	Guangdong
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Taizhou Hospital of Zhejiang	Taizhou	Zhejiang
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Affiliated Cancer Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Plasma concentration of sitravatinib		From first randomization up to 35 months, approximately