A Study of SHR-1701 Plus Bevacizumab and Chemotherapy in Non-Small-Cell-Lung-Cancer

Study Overview
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Brief Summary
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Evaluate efficacy and safety of SHR-1701 in combination with bevacizumab and chemotherapy in advanced or metastatic non-squamous non-small-cell lung cancer with EGFR mutation after failure of TKIs

Official Title
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A Phase 3, Randomized Double-blind, Placebo-controlled, Multicenter Study of SHR-1701 in Combination With Bevacizumab and Chemotherapy in Advanced or Metastatic Non-squamous Non-small-cell Lung Cancer With EGFR Mutation After Failure of TKIs

Conditions
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Advanced or Metastatic Non-squamous Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: SHR-1701 + Pemetrexed Disodium + cisplatin/carboplatin + bevacizumab
* Drug: Placebo + SHR-1701 + Pemetrexed Disodium+ cisplatin/carboplatin
* Drug: Placebo 1 + Placebo 2 +Pemetrexed Disodium + cisplatin/carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - A subject must satisfy all of the following criteria to be considered for inclusion in the study: Histologically or cytologically confirmed advanced or metastatic non-squamous non-small cell lung cancer. Failed with prior EGFR-TKIs treatments. Measurable disease, as defined by RECIST v1.1 The Eastern Cancer Cooperative Group (ECOG) performance status of 0 or 1 Life expectancy ≥ 3 months Adequate hematologic and end-organ function as defined in the protocol Exclusion Criteria: - A subject who meets any of the following criteria will be excluded from study entry: Histologically or cytologically confirmed mixed SCLC and NSCLC. Symptomatic, untreated or active central nervous system metastases. Systemic therapy with immunosuppressive agents within 2 weeks prior to initiation of study treatment With any active autoimmune disease or history of autoimmune disease. Inadequately controlled hypertension. Tumour infiltration into the great vessels on imaging. History of haemoptysis ≥2.5ml per episode within 1 month prior to initiation of study treatment. Uncontrolled tumour-related pain. Patients with active hepatitis B or hepatitis C Severe infections within 4 weeks prior to initiation of study treatment. Active tuberculosis within one year prior to initiation of study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: SHR-1701/ Placebo Plus Chemotherapy With or Without Bevacizumab
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br> | Drug: SHR-1701 + Pemetrexed Disodium + cisplatin/carboplatin + bevacizumab<br>* SHR-1701 + Pemetrexed Disodium + cisplatin/carboplatin + bevacizumab<br>|
| Placebo Comparator: Placebo group 1<br> | Drug: Placebo + SHR-1701 + Pemetrexed Disodium+ cisplatin/carboplatin<br>* Placebo + SHR-1701 + Pemetrexed Disodium+ cisplatin/carboplatin<br>|
| Placebo Comparator: Placebo group 2<br> | Drug: Placebo 1 + Placebo 2 +Pemetrexed Disodium + cisplatin/carboplatin<br>* Placebo 1 + Placebo 2 +Pemetrexed Disodium + cisplatin/carboplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs) as per NCI-CTC AE 5.0 （Stage I） |  | 2 years | 
| BIRC-assessed progression-free survival (PFS) as per RECIST v1.1（Stage II） |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS)（Stage I） |  | 2 years | 
| Objective response rate (ORR)（Stage I） |  | 2 years | 
| Disease control rate (DCR) （Stage I） |  | 2 years | 
| Duration of response (DOR) （Stage I） |  | 2 years | 
| Overall survival (OS) （Stage I） |  | 2 years | 
| Progression free survival (PFS)（Stage II） |  | 2 years | 
| Objective response rate (ORR)（Stage II） |  | 2 years | 
| Disease control rate (DCR)（Stage II） |  | 2 years | 
| Duration of response (DOR) （Stage II） |  | 2 years | 
| Overall survival (OS) （Stage II） |  | 2 years | 
| Incidence and severity of adverse events (AEs), serious adverse events （Stage II） |  | 2 years | 
| (SAEs), and immune-related adverse events (irAEs) as per NCI-CTC AE 5.0（Stage II） |  | 2 years |