A Comparative Study of BAT1706 and EU Avastin® in Patients With Advanced Non Squamous Non Small Cell Lung Cancer

A Multicenter, Randomized, Double Blind, Phase III Study of BAT1706 Versus EU Avastin® Plus Chemotherapy in Patients With Advanced Non Squamous Non Small Cell Lung Cancer

This is a Phase III, randomized, double blind, multicenter, active comparator, parallel two arm study to compare the efficacy, and to evaluate the safety, and immunogenicity of BAT1706 to EU Avastin® in patients with previously untreated advanced non-squamous non-small cell lung cancer (nsNSCLC) to demonstrate clinical equivalence of BAT1706 and EU Avastin®.

Study Overview

• Status: Completed
• Conditions: Non-squamous Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: EU Avastin®; Drug: Paclitaxel; Drug: carboplatin; Drug: BAT1706

• Study Type: Interventional
• Enrollment (Actual): 651
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Xiamen, China
    • The First Affiliated Hospital of Xiamen University
• Mexico
  • Orizaba, Mexico, 94300
    • Clinical Medical Research S.C.
• South Africa
  • Bloemfontein, South Africa, 9301
    • National Hospital Oncology
• Turkey
  • Ankara, Turkey, 6000
    • Baskent University Ankara Hospital
• Ukraine
  • Kryvyi Rih, Ukraine, 53213
    • CI Kryvyi Rih Oncological Dispensary of DRC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Stage IV nsNSCLC or recurrent disease (any Stage at initial diagnosis) no longer amenable to curative surgery or local therapy (histologically or cytologically confirmed).
2. No prior systemic therapy for metastatic disease. Prior systemic therapy and/or radiotherapy for locally advanced disease is permitted if completed ≥ 6 months prior to randomization.
3. Tumors without activating EGFR or ALK mutation. Patients with unknown mutation status or known activating EGFR or ALK mutation may be included provided the corresponding targeted agent is not available and chemotherapy is the standard of care of the study center.
4. At least one measurable target lesion according to RECIST 1.1 (Appendix 13.4) as confirmed by CIR; bone only and brain-only metastases are not allowed. Lesions previously treated with radiotherapy are non-target lesion.
5. Eastern Cooperative Oncology Group performance status of 0 or 1 and life expectancy > 3 months based on Investigator's judgment.

Exclusion Criteria:

1. Diagnosis of small cell carcinoma of the lung, mixed predominant squamous cell carcinoma of the lung, NSCLC not otherwise specified.
2. Tumor cavitation, tumor invading into large blood vessels or close to large vessels with an increased risk of bleeding, according to Investigator's judgment.
3. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGFR, including Avastin®.
4. Prior systemic therapy for metastatic disease.
5. Prior systemic anticancer therapy, or radiotherapy for locally advanced nsNSCLC if completed < 6 months prior to screening.
6. Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre invasive cancer of the cervix.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EU Avastin®; Drug:EU Avastin® 15 mg/kg IV infusions ,every 3 weeks of a cycle for up to 6 cycles, followed for those with non-progressive disease with maintenance monotherapy with Bevacizumab-EU up to a maximum of 8 months. Drug: Paclitaxel 200mg/m² via IV infusions, every 3 weeks of a cycle for up to 6 cycles Drug: Carboplatin AUC 6.0 mg/mL•minute via IV infusions,every 3 weeks of a cycle for up to 6 cycles	Drug: EU Avastin®; 100 mg/4 mL; Drug: Paclitaxel; 200 mg/m²; Drug: carboplatin; target area under the curve [AUC] 6 mg/mL•minute
Experimental: BAT1706; BAT1706 15 mg/kg IV infusions ,every 3 weeks of a cycle for up to 6 cycles, followed for those with non-progressive disease with maintenance monotherapy with BAT1706 up to a maximum of 8 months. Drug: Paclitaxel 200mg/m² via IV infusions, every 3 weeks of a cycle for up to 6 cycles Drug: Carboplatin AUC 6.0 mg/mL•minute via IV infusions,every 3 weeks of a cycle for up to 6 cycles	Drug: Paclitaxel; 200 mg/m²; Drug: carboplatin; target area under the curve [AUC] 6 mg/mL•minute; Drug: BAT1706; 100 mg/4 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	The primary efficacy endpoint is ORR at Week 18 (ORR18) based on tumor response evaluated according to RECIST 1.1 as assessed by CIR. Each patient will be assigned to one of the following RECIST 1.1 categories based on independent CIR, irrespective of protocol deviations or missing data: CR: complete response. PR: partial response. SD: stable disease. PD: progressive disease. NE: not evaluable (insufficient data)	Week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Rate	Progression free survival rate at 12 months, defined as the proportion of patients being alive without documented progression 12 months after randomization, using Kaplan-Meier method.	8 months,1 year and 2 years
Progression Free Survival Time	Progression free survival time defined as the time from the date of randomization to the date of documented clinical or radiological progression or death due to any cause using Kaplan-Meier method.	8 months,1 year and 2 years
Overall Survival Rate	Overall survival rate at 12 months, defined as the proportion of patients being alive 12 months after randomization using Kaplan-Meier method.	8 months,1 year and 2 years
Overall Survival Time	Overall survival time defined as the time from randomization to death of any cause using Kaplan-Meier method.	8 months,1 year and 2 years
Overall Response Rate	ORR at Week 6 (ORR6) and ORR at Week 12 (ORR12), based on tumor response as assessed by CIR, and best ORR of confirmed responses at end of study assessed by local radiologist/Investigator if after Week 18 according to RECIST 1.1.	Week 6 and Week 12
Duration of Response	Duration of response defined as the time from first documentation of a response (CR or PR) and the first documentation of progression (assessed by local radiologist/Investigator if after Week 18) according to RECIST 1.1.	8 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Level of Anti Drug Antibodies (ADA) and Neutralizing Anti-drug Antibodies (NADA) Correlated With Bevacizumab Plasma Level	Plasma level of anti drug antibodies (ADA) and neutralizing anti-drug antibodies (NADA) correlated with bevacizumab plasma level	12 months
Bevacizumab Plasma Exposure Following Treatments of BAT1706 or EU Avastin®	Bevacizumab plasma exposure following treatments of BAT1706 or EU Avastin®	12 months

Collaborators and Investigators

• Sponsor: Bio-Thera Solutions
• Investigators: Study Director: Shengfeng Li, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Actual): November 5, 2019
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: October 20, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: BAT1706-003-CR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No