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CompletedNCT03329911Updated Sep 14, 2021Results posted

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

A Phase 3 interventional study of EU Avastin® and BAT1706 in Non-squamous Non-small Cell Lung Cancer, sponsored by Bio-Thera Solutions. Completed at 5 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-14.

Sponsored by Bio-Thera Solutions · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
651
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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®.

02

Conditions studied

  • Non-squamous Non-small Cell Lung Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
651 participants (actual)

Study arms

  • 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® · Drug: Paclitaxel · Drug: carboplatin

  • 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: BAT1706 · Drug: Paclitaxel · Drug: carboplatin

Interventions

  • DrugEU Avastin®

    100 mg/4 mL

  • DrugBAT1706

    100 mg/4 mL

  • DrugPaclitaxel

    200 mg/m²

  • Drugcarboplatin

    target area under the curve \[AUC\] 6 mg/mL•minute

05

What researchers measure

Primary outcomes

  1. 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)

    Time frame: Week 18

Secondary outcomes

  1. 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.

    Time frame: 8 months,1 year and 2 years

  2. 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.

    Time frame: 8 months,1 year and 2 years

  3. 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.

    Time frame: 8 months,1 year and 2 years

  4. Overall Survival Time

    Overall survival time defined as the time from randomization to death of any cause using Kaplan-Meier method.

    Time frame: 8 months,1 year and 2 years

  5. 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.

    Time frame: Week 6 and Week 12

  6. 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.

    Time frame: 8 months

Other outcomes

  1. 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

    Time frame: 12 months

  2. Bevacizumab Plasma Exposure Following Treatments of BAT1706 or EU Avastin®

    Bevacizumab plasma exposure following treatments of BAT1706 or EU Avastin®

    Time frame: 12 months

06

Results

Posted Sep 13, 2021

Participant flow

Participant flow — Overall Study
MilestoneEU Avastin®BAT1706
Started326325
Completed209222
Not completed117103

Outcome measures

PrimaryOverall 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)

Time frame:
Week 18
Reported as:
Count of participants · Participants
Overall Response Rate
ParticipantsEU Avastin®BAT1706
Overall Response Rate156145
SecondaryProgression 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.

Time frame:
8 months,1 year and 2 years

Results for this outcome have not been posted.

SecondaryProgression 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.

Time frame:
8 months,1 year and 2 years

Results for this outcome have not been posted.

SecondaryOverall Survival Rate

Overall survival rate at 12 months, defined as the proportion of patients being alive 12 months after randomization using Kaplan-Meier method.

Time frame:
8 months,1 year and 2 years

Results for this outcome have not been posted.

SecondaryOverall Survival Time

Overall survival time defined as the time from randomization to death of any cause using Kaplan-Meier method.

Time frame:
8 months,1 year and 2 years

Results for this outcome have not been posted.

SecondaryOverall 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.

Time frame:
Week 6 and Week 12

Results for this outcome have not been posted.

SecondaryDuration 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.

Time frame:
8 months

Results for this outcome have not been posted.

Other pre-specifiedPlasma 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

Time frame:
12 months

Results for this outcome have not been posted.

Other pre-specifiedBevacizumab Plasma Exposure Following Treatments of BAT1706 or EU Avastin®

Bevacizumab plasma exposure following treatments of BAT1706 or EU Avastin®

Time frame:
12 months

Results for this outcome have not been posted.

Adverse events

Collected over From the start of the first study medication administration until 28 days after discontinuation/completion of the study medication or up to Week 53 after randomization- All AEs, regardless of relationship to the study medication/study procedures. During the LTE study, only adverse events of special interest (AESIs) and SAEs until 28 days after the subject's last dose will be collected.. Non-serious events are listed at a 0.3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
EU Avastin®4/324 (1.2%)119/324 (36.7%)8/324 (2.5%)
BAT17067/325 (2.2%)119/325 (36.6%)9/325 (2.8%)
Most frequent serious events
Most frequent serious events
EventEU Avastin®BAT1706
Blood and lymphatic system disordersBlood and lymphatic system disorders46/32431/325
Infections and infestationsInfections and infestations22/32427/325
Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders19/32421/325
Gastrointestinal disordersGeneral disorders12/32412/325
Cardiac disordersCardiac disorders4/32411/325
Vascular disordersVascular disorders8/3245/325
General disorders and administration site conditionsGastrointestinal disorders4/3248/325
Nervous system disordersNervous system disorders4/3244/325
Most frequent other events
Most frequent other events
EventEU Avastin®BAT1706
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders3/3245/325
Renal and urinary disordersRenal and urinary disorders2/3243/325
Neoplasms benign, malignant and unspecified (inclcysts and polyps)Neoplasms benign, malignant and unspecified (incl cysts and polyps)2/3240/325
HepatobiliarydisordersHepatobiliary disorders1/3241/325

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)EU Avastin®BAT1706Total
<=18 years000
Between 18 and 65 years208233441
>=65 years11892210
Age, Continuous
Age, Continuous(years)EU Avastin®BAT1706Total
Median60 (26 to 88)61 (27 to 84)61 (26 to 88)
Sex: Female, Male
Sex: Female, Male(Participants)EU Avastin®BAT1706Total
Female9797194
Male229228457
Race (NIH/OMB)
Race (NIH/OMB)(Participants)EU Avastin®BAT1706Total
American Indian or Alaska Native131124
Asian140141281
Native Hawaiian or Other Pacific Islander101
Black or African American112
White171172343
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)EU Avastin®BAT1706Total
Turkey6764131
China139140279
Ukraine98102200
South Africa628
Mexico161733
07

Study locations

5 sites
  • The First Affiliated Hospital of Xiamen University
    Xiamen, China
  • Clinical Medical Research S.C.
    Orizaba, 94300, Mexico
  • National Hospital Oncology
    Bloemfontein, 9301, South Africa
  • Baskent University Ankara Hospital
    Ankara, 6000, Turkey
  • CI Kryvyi Rih Oncological Dispensary of DRC
    Kryvyi Rih, 53213, Ukraine
08

References and documents

Study documents

  • Study protocol · Jun 20, 2019
  • Statistical analysis plan · Nov 28, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03329911
Lead sponsor
Bio-Thera Solutions
Responsible party
Sponsor
First posted
Nov 6, 2017
Start date
Oct 20, 2017
Primary completion
Nov 5, 2019
Completion
May 27, 2021
Results posted
Sep 13, 2021
Last update
Sep 14, 2021

Study contacts

Shengfeng Li
study director · Sponsor GmbH

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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