Clinical trial NCT05001724: KN046 Plus Lenvatinib in Subject With Advanced Non-Small Cell Lung Cancer in the Failure of Anti-PD-(L)1 Agent
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Advanced Non-small Cell Lung Cancer
Lead sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-08-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 .


Eligibility criteria: 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.

Primary outcomes:
measure: DLT
timeFrame: 28 days or 21 days
measure: OS
timeFrame: up to 2 years
measure: PFS
timeFrame: up to 2 years
Secondary outcomes:
measure: ORR
timeFrame: up to 2 years
measure: DCR
timeFrame: up to 2 years
measure: DOR
timeFrame: up to 2 years
measure: CBR
timeFrame: up to 2 years
measure: TTR
timeFrame: up to 2 years
Other outcomes:
measure: Safety endpoint
timeFrame: up to 2 years
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Caicun Zhou, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: