Phase Ib/II Study of SHR-8068 Injection in the Treatment of Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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To evaluate the tolerability and safety of SHR-8068 in combination with adebrelimab in subjects with advanced NSCLC To evaluate the efficacy of SHR-8068 in combination with adebrelimab and platinum-based chemotherapy in subjects with advanced NSCLC

Official Title
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An Open-label, Multicenter Phase Ib/II Clinical Study of SHR-8068 Combined With Adebrelimab and Platinum-based Chemotherapy in the Treatment of Advanced Non-small Cell Lung Cancer

Conditions
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Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: SHR-8068；Adebrelimab
* Drug: SHR-8068；adebrelimab and platinum-based chemotherapy
* Drug: Adebrelimab；platinum-based chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 75 years old, both male and female Stage 1: pathologically diagnosed, incurable NSCLC subjects who have failed standard treatment Stage 2: have a histologically or cytologically confirmed diagnosis of relapsed or metastatic NSCLC; have not received prior systemic treatment for their recurrent or metastatic NSCLC; PD-L1 TPS <50% as confirmed by central laboratory At least one measurable lesion based on RECIST v1.1 criteria ECOG PS score: 0-1 points Expected survival period ≥ 3 months Good levels of organ function Patients voluntarily joined the study and signed informed consent Exclusion Criteria: Patients with EGFR activating mutation, positive ALK fusion gene or known ROS1 fusion gene Untreated brain metastases; or associated with meningeal metastases, spinal cord compression, etc. Uncontrolled pleural, pericardial, or ascites with clinical symptoms Severe bone damage caused by tumor bone metastasis Suffering from other malignant tumors in the past 3 years or at the same time Presence of any active or known autoimmune disease Systemic treatment with corticosteroids or other immunosuppressants within 2 weeks before the first dose Have clinical symptoms or diseases of the heart that are not well controlled Serious infection occurred within 1 month before the first dose Past or current active interstitial lung disease requiring treatment, non-infectious pneumonia requiring glucocorticoid system treatment; current active pneumonia or pulmonary function test confirmed severe impairment of pulmonary function With active pulmonary tuberculosis Known positive history of human immunodeficiency virus test or acquired immunodeficiency syndrome, known active viral hepatitis Known history of inflammatory bowel disease Inoculated with live attenuated vaccine within 28 days before the first dose Known allergic reaction to other monoclonal antibodies Received >30 Gy of pulmonary radiotherapy within 6 months before the first dose; received major surgical treatment, systemic chemotherapy, immunotherapy or other clinical trial drugs within 4 weeks before the first dose; within 2 weeks before the first dose Received palliative radiotherapy; oral molecularly targeted drugs, discontinued to less than 5 half-lives before first dose; failure to recover from toxicity and/or complications of previous interventions to NCI-CTC AE ≤1 degree According to the judgment of the researcher, there are other factors that may affect the results of the study or cause the study to be terminated halfway.

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: This study is a multicenter, open-label, dose-finding and efficacy-expansion phase Ib/II study. The first stage is for dose finding, using modified 3+3 design; the second stage is for dose confirmation and efficacy expansion through randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-8068 in combination with adebrelimab<br> | Drug: SHR-8068；Adebrelimab<br>* SHR-8068: Sterile Injection, 50mg/10mL, Intravenous Infusion Adebrelimab: injection, 600mg/12mL, intravenous infusion<br>|
| Experimental: SHR-8068 in combination with adebrelimab and platinum-based chemotherapy<br> | Drug: SHR-8068；adebrelimab and platinum-based chemotherapy<br>* SHR-8068: Intravenous Infusion Adebrelimab: injection, intravenous infusion Pemetrexed disodium for injection: , intravenous drip Paclitaxel for injection (albumin-bound): intravenous drip Paclitaxel injection: intravenous drip Carboplatin injection: intravenous drip Cisplatin injection: intravenous drip<br>|
| Experimental: Adebrelimab in combination with platinum-based chemotherapy<br> | Drug: Adebrelimab；platinum-based chemotherapy<br>* Adebrelimab: intravenous infusion Pemetrexed disodium for injection: intravenous drip Paclitaxel for injection (albumin-bound): intravenous drip Paclitaxel injection: intravenous drip Carboplatin injection: intravenous drip Cisplatin injection: intravenous drip<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity |  | The observation period is 21 days after the first dose | 
| 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 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate, determined using RECIST v1.1 criteria |  | up to 2 years | 
| Progression-Free-Survival assessed by investigator |  | up to 2 years |