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

Phase 3

Terminated

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Interventions: Drug: Docetaxel
Drug: Tislelizumab
Drug: Sitravatinib

Registration Number: NCT04921358

Lead Sponsor: BeiGene

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 377

Inclusion Criteria

Metastatic or unresectable locally advanced histologically or cytologically confirmed Non-Small Cell Lung Cancer (NCSLC), not amenable to treatment with curative intent
Able to provide archival/fresh tumor tissues for biomarker analysis to assess PD-L1 expression and other biomarkers.
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
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.
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)
At least 1 measurable lesion as defined based on RECIST v1.1 by investigator

Key

Exclusion Criteria

Has received docetaxel as monotherapy or in combination with other therapies.
Squamous NSCLC with central cavitation, or NSCLC with hemoptysis (> 50 mL/day)
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.
Active leptomeningeal disease for metastatic NSCLC, or uncontrolled or untreated brain metastasis.
Active autoimmune diseases or history of autoimmune diseases that may relapse.

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Docetaxel	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.
Tislelizumab + Sitravatinib	Tislelizumab	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.
Tislelizumab + Sitravatinib	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival (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).	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.
Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)	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).	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) as Assessed by the Investigator	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).	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.
Overall Response Rate (ORR)	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).	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.
Duration of Response (DOR)	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).	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.
Disease Control Rate (DCR)	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).	Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or stable disease per RECIST v1.1.
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	Baseline and Cycle 5 Day 1 (Week 12) and Cycle 7 Day 1 (Week 18)	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.
Change From Baseline in EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Coughing, Dyspnoea, and Chest Pain Scales	Baseline and Cycle 5 Day 1 (Week 12) and Cycle 7 Day 1 (Week 18)	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.
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS)	Baseline and Cycle 5 Day 1 (Week 12) and Cycle 7 Day 1 (Week 18)	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.
Number of Participants With Adverse Events	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).	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

Trial Locations

Locations (61): Blacktown Cancer and Haematology Centre
🇦🇺
Blacktown, New South Wales, Australia
Campbelltown Hospital
🇦🇺
Campbelltown, New South Wales, Australia
The Tweed Valley Hospital
🇦🇺
Cudgen, New South Wales, Australia
St George Hospital
🇦🇺
Kogarah, New South Wales, Australia
Pindara Private Hospital
🇦🇺
Benowa, Queensland, Australia
Cancer Research South Australia
🇦🇺
Adelaide, South Australia, Australia
Monash Health
🇦🇺
Clayton, Victoria, Australia
St Vincents Hospital Melbourne
🇦🇺
Fitzroy, Victoria, Australia
Sunshine Hospital
🇦🇺
St Albans, Victoria, Australia
Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
🇨🇳
Hefei, Anhui, China
Scroll for more (51 remaining)
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia