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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Docetaxel
* Drug: Sitravatinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Metastatic or unresectable locally advanced histologicallyor 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Tislelizumab in combination with Sitravatinib<br>tislelizumab 200 mg intravenously once every 3 weeks in combination with sitravatinib 100 mg orally once a day | Drug: Tislelizumab<br>* administered intravenously<br>Drug: Sitravatinib<br>* administered orally<br>|
| Active Comparator: Arm B: Docetaxel<br>docetaxel 75 mg/m2 intravenously once every 3 weeks | Drug: Docetaxel<br>* administered intravenously<br>|

What is the study measuring?
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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 |