A Study of Fluzoparib (SHR-3162) and Temozolomide With or Without SHR-1316 in Treating Patients With Replapsed Small Cell Lung Cancer

Study Overview
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Brief Summary
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This research study is a multicentre phase Ⅰb/Ⅱ Study to evaluate the efficacy and safety of the combination of Fluzoparib (SHR-3162) and temozolomide with or without SHR-1316 in small cell lung cancer

Official Title
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A Phase Ⅰb/Ⅱ Study of Fluzoparib (SHR-3162) and Temozolomide With or Without SHR-1316 in Treating Patients With Replapsed Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Fluzoparib
* Drug: temozolomide
* Biological: SHR-1316


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have recurrent small cell lung cancer confirmed by histology or cytology. Failed one prior line of platinum-based chemotherapy. Subjects must have measurable disease, at least one lesion, by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria (within 28 days prior to administration of study treatment) ; Freshly acquired samples or archived specimens within 12 months before randomization must be provided. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Participant must have a life expectancy ≥ 12 weeks. Exclusion Criteria: Active or untreated central nervous system (CNS) metastases. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. History of autoimmune disease. Positive test result for human immunodeficiency virus (HIV). Active hepatitis B or hepatitis C. Severe infections. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Significant cardiovascular disease. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Fluzoparib (SHR-3162) combined with temozolomide or Fluzoparib (SHR-3162) and temozolomide with SHR-1316
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental A (part 1) : Fluzoparib + temozolomide<br> | Drug: Fluzoparib<br>* Given PO<br>Drug: temozolomide<br>* Given PO<br>|
| Experimental: Experimental B (part 2) : Fluzoparib + temozolomide + SHR-1316<br> | Drug: Fluzoparib<br>* Given PO<br>Drug: temozolomide<br>* Given PO<br>Biological: SHR-1316<br>* Given injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ⅰb: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period. |  | At the end of Cycle1 (each cycle is 21 days ) | 
| Phase Ⅰb: Determination of Recommended Phase II dose (RP2D) of Escalating Dose of Fluzoparib and temozolomide with or without SHR-1316. |  | Up to approximately 2 Years | 
| Phase Ⅱ: Progression Free Survival (PFS) at four months. |  | Up to approximately 2 Years | 
| Phase Ⅱ: Progression Free Survival (PFS) as Assessed by the Investigator according to RECIST v1.1. | Progression Free Survival, defined as the time from randomization to first assessment of disease progression or death, whichever is earlier. | Up to approximately 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective Response Rate, determined using RECIST v1.1 criteria, defined as best overall response (complete or partial response) across all assessment time points. | up to approximately 2 Years | 
| Duration of Response | Duration of Response, determined using RECIST v1.1 criteria. | Up to approximately 2 Years | 
| Disease Control Rate | Disease Control Rate, determined using RECIST v1.1 criteria. | Up to approximately 2 Years | 
| Time to Response | Time to Response, defined as the time from randomization to PR or CR. | Up to approximately 2 Years | 
| Overall survival and overall survival at 6 months, 9months and 12 months | Overall survival is the time interval from the date of randomization to death due to any reason or lost of follow-up. | Up to approximately 1 Year |