Non-squamous Non-small Cell Lung Cancer
Conditions
Brief 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®.
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
Sponsors
Bio-Thera Solutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Week 18 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate | 8 months,1 year and 2 years | 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. |
| Progression Free Survival Time | 8 months,1 year and 2 years | 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. |
| Overall Survival Rate | 8 months,1 year and 2 years | Overall survival rate at 12 months, defined as the proportion of patients being alive 12 months after randomization using Kaplan-Meier method. |
| Overall Response Rate | Week 6 and Week 12 | 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. |
| Duration of Response | 8 months | 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. |
| Overall Survival Time | 8 months,1 year and 2 years | Overall survival time defined as the time from randomization to death of any cause using Kaplan-Meier method. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma Level of Anti Drug Antibodies (ADA) and Neutralizing Anti-drug Antibodies (NADA) Correlated With Bevacizumab Plasma Level | 12 months | Plasma level of anti drug antibodies (ADA) and neutralizing anti-drug antibodies (NADA) correlated with bevacizumab plasma level |
| Bevacizumab Plasma Exposure Following Treatments of BAT1706 or EU Avastin® | 12 months | Bevacizumab plasma exposure following treatments of BAT1706 or EU Avastin® |
Countries
China, Mexico, South Africa, Turkey (Türkiye), Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
EU Avastin®: 100 mg/4 mL
Paclitaxel: 200 mg/m²
carboplatin: target area under the curve \[AUC\] 6 mg/mL•minute | 326 |
| 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
BAT1706: 100 mg/4 mL
Paclitaxel: 200 mg/m²
carboplatin: target area under the curve \[AUC\] 6 mg/mL•minute | 325 |
| Total | 651 |
Baseline characteristics
| Characteristic | EU Avastin® | BAT1706 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 118 Participants | 92 Participants | 210 Participants |
| Age, Categorical Between 18 and 65 years | 208 Participants | 233 Participants | 441 Participants |
| Age, Continuous | 60 years | 61 years | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 13 Participants | 11 Participants | 24 Participants |
| Race (NIH/OMB) Asian | 140 Participants | 141 Participants | 281 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 171 Participants | 172 Participants | 343 Participants |
| Region of Enrollment China | 139 participants | 140 participants | 279 participants |
| Region of Enrollment Mexico | 16 participants | 17 participants | 33 participants |
| Region of Enrollment South Africa | 6 participants | 2 participants | 8 participants |
| Region of Enrollment Turkey | 67 participants | 64 participants | 131 participants |
| Region of Enrollment Ukraine | 98 participants | 102 participants | 200 participants |
| Sex: Female, Male Female | 97 Participants | 97 Participants | 194 Participants |
| Sex: Female, Male Male | 229 Participants | 228 Participants | 457 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 324 | 7 / 325 |
| other Total, other adverse events | 8 / 324 | 9 / 325 |
| serious Total, serious adverse events | 119 / 324 | 119 / 325 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EU Avastin® | Overall Response Rate | 156 Participants |
| BAT1706 | Overall Response Rate | 145 Participants |
Secondary
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
Secondary
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
Secondary
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
Secondary
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
Secondary
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
Secondary
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
Other Pre-specified
Bevacizumab Plasma Exposure Following Treatments of BAT1706 or EU Avastin®
Bevacizumab plasma exposure following treatments of BAT1706 or EU Avastin®
Time frame: 12 months
Other Pre-specified
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