KN046 Plus Lenvatinib in Subject With Advanced Non-Small Cell Lung Cancer in the Failure of Anti-PD-(L)1 Agent

Study Overview
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Brief Summary
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This is a phase 2/3, multicenter, randomized, open, positive-controlled study of patients with advanced non-small cell lung cancer whose disease has progressed after prior anti-PD-(L)1 therapy. Subjects should have documented progressive disease during prior treatment with first- or second-line PD-(L)1 and platinum-containing dual-agent chemotherapy.Subjects will be randomized to two treatment groups in a 1:1 ratio. Treatment Group: KN046 5mg/kg Q3W + lenvatinib recommended for phase III dose (RP3D) every day. Control group: Docetaxel 75mg/m2 Q3W .

Official Title
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A Randomized, Open-Label, Active-Controlled, Multi-Center Study to Compare Efficacy, Safety, and Tolerability of KN046 Combined With Lenvatinib Versus Docetaxel in Subjects With Non-Small Cell Lung Cancer After Failure of Anti-PD-(L)1 Agent

Conditions
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Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: KN046
* Drug: Lenvatinib
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Has a histologically confirmed or cytologically confirmed diagnosis of advanced NSCLC; Non-squamous non-small cell lung cancer, no EGFR mutation or ALK rearrangement or ROS1 fusion, no known RET fusion or MET14 exon jump mutation; Squamous non-small cell lung cancer with no known EGFR mutation or ALK rearrangement or ROS1 fusion /RET fusion /MET14 exon jump mutation; Has received prior systemic treatment with first- or second-line PD-(L)1 and platinum-containing dual-agent chemotherapy for their advanced NSCLC; Has measurable disease; Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status; Has adequate organ function; Has a life expectancy of at least 3 months; If female of childbearing potential, have a negative serum pregnancy test within 7 days prior to first trial treatment; If female of childbearing potential or a male subject with a partner with childbearing potential, be willing to use a highly effective method of contraception (with a failure rate of less than 1.0% per year) from first study treatment to 24 weeks after completion of the trial treatment. Exclusion Criteria: Untreated active central nervous system metastasis or leptomeningeal metastasis; Is currently participating and receiving an investigational drug or has participated in a study of an investigational drug within 4 weeks or within 5 times of half-life (no less than 2 weeks), whichever is shorter prior to the first dose of trial treatment; Major surgery for any reason, except diagnostic biopsy, within 4 weeks of the first administration of trial treatment and/or if the subject has not fully recovered from the surgery within 4 weeks of the first administration of trial treatment; Curative radiation within 3 months of the first dose of trial treatment; Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement doses, equivalent to < 10 mg prednisone daily, inhaled steroids and topical use of steroids); Vaccination within 28 days of the first administration of trial treatment, except for administration of inactivated vaccines; Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management; History or current active autoimmune disease that might deteriorate when receiving an immunostimulatory agent; Previous malignant disease; History of uncontrolled intercurrent illness; Prior therapy with any antibody/drug targeting T cell coregulatory proteins; Has received treatment with lenvatinib or docetaxel or VEGFR-TKI; Known severe hypersensitivity reactions to antibody drug; Is pregnant or breastfeeding; Other medical conditions that at the discretion of investigator interfere with the requirements of the trial in terms of safety or efficacy evaluation, or treatment compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Cohort 1: KN046 plus Lenvatinib RP3D.<br>Experimental arm: Cohort 1: KN046 5mg/kg every 3 weeks + lenvatinib RP3D every day until progressive disease or unacceptable toxicity. | Biological: KN046<br>* KN046 is 5 milligram per kilogram, every 3 weeks.<br>Drug: Lenvatinib<br>* Lenvatinib is RP3D milligram per day, every day.<br>|
| Active Comparator: Docetaxel<br>Active Comparator: docetaxel 75 mg/m² every 3 weeks until progressive disease or unacceptable toxicity. | Drug: Docetaxel<br>* Docetaxel is 75 milligram per Square meter, every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Dose limit toxicity (phase 2) | 28 days or 21 days | 
| OS | Overall survival (OS) was defined as the time from randomization to death due to any cause (phase 3). | up to 2 years | 
| PFS | Progression-free survival (PFS) was defined as the time from randomization grouping to the first documented disease progression or death from any cause as evaluated by the investigator according to RECIST 1.1 criteria (phase 3). | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate (ORR) based on the RECIST 1.1 by principal investigator | up to 2 years | 
| DCR | Disease control rate (DCR) based on the RECIST 1.1 by principal investigator | up to 2 years | 
| DOR | Duration of response (DOR) based on the RECIST 1.1 by principal investigator | up to 2 years | 
| CBR | Clinical benefit rate (CBR) based on the RECIST 1.1 by independent review committee | up to 2 years | 
| TTR | Time to response (TTR) based on the RECIST 1.1 by independent review committee | up to 2 years |