AK112 in Combination With Chemotherapy in Advanced Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This trial is a Phase III study. All patients are stage IIIB/C (unsuitable for radical therapy) or stage IV squamous non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 combined with chemotherapy versus Tislelizumab combined with chemotherapy in patients with advanced squamous NSCLC.

Official Title
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A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Combined With Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer

Conditions
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Advanced Squamous Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AK112, Carboplatin, Paxlitaxel
* Drug: Tislelizumab, Carboplatin, Paxlitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures). ≥18 years old(at the time consent is obtained). Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Has a life expectancy of at least 3 months. Has a histologically or cytologically confirmed diagnosis of squamous NSCLC. Has Stage IIIB/C or IV NSCLC (American Joint Committee on Cancer [AJCC]). Has no prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Has adequate organ function. Exclusion Criteria: Histological diagnosis of non-squamous NSCLC. Has EGFR-sensitive mutations or ALK gene translocations. Known ROS1 rearrangement, MET exon 14 skipping mutation, or RET gene fusion positivite. Is currently participating in a study of an investigational agent or using an investigational device. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment. Has undergone major surgery within 30 days of Study Day 1. Has known active central nervous system (CNS) metastases. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Has an active infection requiring systemic therapy. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. Has received a live virus vaccine within 30 days of the planned first dose of study therapy. Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: AK112 in Combination With Paclitaxel Plus Carboplatin<br>AK112 will be administered at a selected dose intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles. | Drug: AK112, Carboplatin, Paxlitaxel<br>* IV infusion,Specified dose on specified days<br>|
| Active Comparator: Active Comparator: Tislelizumab in Combination With Paclitaxel Plus Carboplatin<br>Tislelizumab will be administered at a dose of 200 mg intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles. | Drug: Tislelizumab, Carboplatin, Paxlitaxel<br>* IV infusion,Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS assessed by IRRC per RECIST v1.1 | Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the blinded IRRC or death due to any cause (whichever occurs first). | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival (OS) is defined as the time from the start of treatment with AK112 until death due to any cause. | Up to approximately 2 years | 
| ORR assessed by IRRC per RECIST v1.1 | ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1. | Up to approximately 2 years | 
| DoR assessed by IRRC per RECIST v1.1 | Duration of response (DoR) assessed according to RECIST v1.1 | Up to approximately 2 years | 
| DCR assessed by IRRC per RECIST v1.1 | Disease control rate (DCR) assessed according to RECIST v1.1. | Up to approximately 2 years | 
| TTR assessed by IRRC per RECIST v1.1 | Time to response (TTR) is defined as the time to response base on RECIST v1.1. | Up to approximately 2 years | 
| PFS assessed by investigator per RECIST v1.1 | Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression assessed by the investigator or death due to any cause (whichever occurs first). | Up to approximately 2 years | 
| ORR assessed by the investigator per RECIST v1.1 | ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1. | Up to approximately 2 years | 
| DoR assessed by the investigator per RECIST v1.1 | Duration of response (DoR) assessed according to RECIST v1.1. | Up to approximately 2 years | 
| DCR assessed by the investigator per RECIST v1.1 | Disease control rate (DCR) assessed according to RECIST v1.1. | Up to approximately 2 years | 
| TTR assessed by the investigator per RECIST v1.1 | Time to response (TTR) is defined as the time to response base on RECIST v1.1. | Up to approximately 2 years | 
| AE | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to approximately 2 years | 
| ADA | Number of subjects with detectable anti-drug antibodies (ADA). | Up to approximately 2 years | 
| Cmax and Cmin | AK112 serum drug concentrations in subjects at different time points after AK112 administration | Up to approximately 2 years | 
| PD-L1 expression | The correlationship between PD-L1 expression and efficacy. | Up to approximately 2 years |