Study of KN046 With Chemotherapy in First Line Advanced NSCLC

Study Overview
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Brief Summary
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This is a phase II study of KN046 plus platinum-based doublet chemotherapy in previously untreated advanced non-squamous and squamous NSCLC subjects. The study will assess primarily the safety and efficacy of KN046 plus platinum-based doublet chemotherapy.

Official Title
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An Open-label, Phase II Study of KN046 Evaluating the Efficacy and Safety of KN046 Plus Platinum-based Doublet Chemotherapy as First Line Therapy in Advanced Non-small Cell Lung Cancer Subjects.

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: KN046
* Drug: Paclitaxel
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has a histologically or cytologically confirmed diagnosis of stage IV NSCLC; Has not received prior systemic treatment for metastatic NSCLC; Has measurable disease based on RECIST 1.1. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status. Has adequate organ function. Has provided tumor tissue from locations not radiated prior to biopsy. Key Exclusion Criteria: Previous immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) Previously untreated or symptomatic central nervous system (CNS) metastases Has received a live-virus vaccination within 28 days of planned treatment start. Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody and chemotherapy. Has or had active autoimmune disease.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN046 + carboplatin/paclitaxel<br>KN046 5 mg/kg IV every three weeks (Q3W) +Carboplatin AUC5 IV Q3W x 4 cycles + Paclitaxel 500 mg/m2 IV Q3W x 4 cycles | Biological: KN046<br>* IV infusion<br>Drug: Paclitaxel<br>* IV infusion<br>Drug: Carboplatin<br>* IV infusion<br>|
| Experimental: KN046 + carboplatin/pemetrexed<br>KN046 5 mg/kg IV Q3W +Carboplatin AUC5 IV Q3W x 4 cycles + Pemetrexed 500 mg/m2 IV Q3W x 4 cycles | Biological: KN046<br>* IV infusion<br>Drug: Pemetrexed<br>* IV infusion<br>Drug: Carboplatin<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1. ORR. | Up to approximately 12 months | 
| Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death. | Up to approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced a treatment-emergent adverse event (TEAE) | TEAE was defined any treatment emergent adverse event. | Up to approximately 12 months | 
| Number of Participants Who Experienced an immune-related AE (irAE) | irAE was defined any immune-related adverse event (AE). | Up to approximately 12 months |