mil60 Versus Bevacizumab in Patients With Treatment-naïve Non-squamous Non-small Cell Lung Cancer

Efficacy and Safety of First-line mil60 Plus Paclitaxel/Carboplatin Versus Bevacizumab Plus Paclitaxel/Carboplatin in Patients With Advanced and Recurrent Non-squamous Non-small Cell Lung Cancer: a Randomized, Double-blind, Phase 3 Study

This randomized, double-blind, multi-center phase 3 study is aimed to compare the efficacy and safety of mil60 with bevacizumab as first-line treatment when combined with standard chemotherapy (paclitaxel/carboplatin) in treatment-naive patients with advanced or recurrent non-squamous NSCLC.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: mil60; Drug: Bevacizumab

Detailed Description

This is a multicenter, double-blind, randomized, parallel-group Phase 3 clinical trial evaluating the efficacy and safety of mil60 plus paclitaxel and carboplatin versus bevacizumab plus paclitaxel and carboplatin in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC.The primary objective of the study was to compare the Objective Response Rate according to RECIST 1.1 of mil60 in combination with paclitaxel plus carboplatin and bevacizumab plus paclitaxel plus carboplatin in the treatment of advanced or recurrent non-squamous NSCLC subjects.

• Study Type: Interventional
• Enrollment (Actual): 517
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Cancer Institute/Hospital, Chinese Academy of Medical Sciences
  • Shenzhen, China
    • Peking University Shenzhen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed inform consent form(ICF)
• Aged 18-75 years, male or female
• Histologically or cytologically documented inoperable, local advanced (stage IIIB), metastatic (stage IV), or recurrent non-squamous NSCLC
• At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1
• Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Patients of childbearing potential must agree to use effective contraceptive measures during study treatment and for 6 months after receiving last study treatment

Exclusion Criteria:

• Mixed non-small cell lung cancer with squamous cell carcinoma component, or small cell carcinoma
• Patients with known Anaplastic Lymphoma Kinase（ALK） or C-Ros Oncogene 1 Receptor Tyrosine Kinase （ROS1）rearrangement
• History of hemoptysis within 3 months prior to screening with blood volume more than 2.5 mL
• Evidence of tumor invading major blood vessels on imaging
• Patients with brain metastasis, spinal cord compression or carcinomatous meningitis history
• Uncontrolled hypertension, prior history of hypertensive crisis and hypertensive encephalopathy
• Clinically significant cardiovascular disease but not limited to active infections; unstable angina; stroke or transient cerebral ischemia; myocardial infarction; congestive heart-failure; serious cardiac arrhythmia, hepatic, renal or metabolic disease requiring medication during the study
• History of radical radiotherapy to the thorax within 6 months
• Serious, non-healing wound, active ulcer, or untreated bone fracture, or major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during the course of the study
• Recent or current treatment with aspirin or other non-steroidal anti-inflammatory drugs (NSAID) known to inhibit platelet function within 10 days prior to first dose of study treatment
• Recent or current treatment with anticoagulants or thrombolytic agent within 10 days prior to first dose of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mil60; mil60 (15mg/kg) was co-administered intravenously with 4 to 6-cycle paclitaxel/carboplatin, non-progressive patients are then given with maintenance single-agent mil60 (7.5mg/kg) until disease progression, intolerable toxicity, or withdrawal.	Drug: mil60; 15mg/kg in combination with paclitaxel/carboplatin for 6 cycles, then maintains at 7.5mg/kg; Other Names: No other intervention name
Active Comparator: Bevacizumab; Bevacizumab (15mg/kg) was co-administered intravenously with 4 to 6-cycle paclitaxel/carboplatin, non-progressive patients are then given with maintenance single-agent mil60 (7.5mg/kg) until disease progression, intolerable toxicity, or withdrawal.	Drug: Bevacizumab; 15mg/kg in combination with paclitaxel/carboplatin for 6 cycles, then switched to mil60 at 7.5mg/kg; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Percentage of patients with complete remission or partial response	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Percentage of patients with complete remission or partial response	26 months
Duration of response	Interval from the onset of a complete remission or partial response until evidence of disease progression or death	24 months
Progression-free survival	Interval between randomization and disease progression or death	24 months
Disease control rate	Percentage of patients with complete remission, partial response and stable disease	24 months
Overall survival	the time from randomisation to death from any cause	30 months

Collaborators and Investigators

• Sponsor: Beijing Mabworks Biotech Co., Ltd.
• Collaborators: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Jie Wang, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Wan R, Dong X, Chen Q, Yu Y, Yang S, Zhang X, Zhang G, Pan Y, Sun S, Zhou C, Hong W, Zhao H, Yang L, Huang L, Wu R, Zang A, Ma R, Wu L, Lv D, Fu X, Han J, Li W, Duan J, Wang K, Jiang O, Chen Y, Guo Z, Gao H, Wen J, Wang S, Zhao E, Li G, Yue L, Liang L, Zeng A, Wang X, Zhu Y, Pan H, Dai Z, Feng W, Zhao G, Lin C, Li C, Li N, Bao Y, Li Y, Su Y, Zhao M, Fang H, Zhu Y, Zhang Y, Ding L, Wang Y, Yuan X, Wang J. Efficacy and safety of MIL60 compared with bevacizumab in advanced or recurrent non-squamous non-small cell lung cancer: a phase 3 randomized, double-blind study. EClinicalMedicine. 2021 Nov 19;42:101187. doi: 10.1016/j.eclinm.2021.101187. eCollection 2021 Dec.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2017
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 28, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: mil60-CT02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No