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

NCT05001724 | Terminated Phase 2

• 1 other identifier: KN046-302
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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 .

Conditions

Advanced Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• ORR

  up to 2 years

• DCR

  up to 2 years

• DOR

  up to 2 years

• CBR

  up to 2 years

• TTR

  up to 2 years

Other Outcomes (1)

• Safety endpoint

  up to 2 years

Study Arms (2)

Cohort 1: KN046 plus Lenvatinib RP3D.

EXPERIMENTAL

Experimental arm: Cohort 1: KN046 5mg/kg every 3 weeks + lenvatinib RP3D every day until progressive disease or unacceptable toxicity.

Biological: KN046; Drug: Lenvatinib

Docetaxel

ACTIVE COMPARATOR

Active Comparator: docetaxel 75 mg/m² every 3 weeks until progressive disease or unacceptable toxicity.

Drug: Docetaxel

Interventions

KN046 BIOLOGICAL

KN046 is 5 milligram per kilogram, every 3 weeks.

Cohort 1: KN046 plus Lenvatinib RP3D.

Lenvatinib DRUG

Lenvatinib is RP3D milligram per day, every day.

Cohort 1: KN046 plus Lenvatinib RP3D.

Docetaxel DRUG

Docetaxel is 75 milligram per Square meter, every 3 weeks.

Docetaxel

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Interventions

lenvatinib; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Caicun Zhou, MD,PhD

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: August 12, 2021
• Study Start: October 28, 2021
• Primary Completion: February 13, 2023
• Study Completion: April 7, 2023
• Last Updated: April 25, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)