A Study to Compare the Similarity in Efficacy and Safety Between TRS003 and China-approved Bevacizumab® in NSCLC
- Conditions
- Advanced Non-squamous Non-small-cell Lung Cancer
- Interventions
- Registration Number
- NCT04416035
- Lead Sponsor
- Zhejiang Teruisi Pharmaceutical Inc.
- Brief Summary
This is a double-blind Phase 3 clinical trial evaluating the efficacy and safety of TRS003 and paclitaxel-carboplatin versus China-approved bevacizumab and paclitaxel-carboplatin in patients with unresectable, locally advanced, or metastatic non-squamous non-small cell lung cancer (NSCLC). Approximately 608 patients will be enrolled in this study from America, Europe, and Asia. Patients who sign the informed consent and meet the inclusion criteria, will be randomized (1:1) to receive either TRS003 in combination with paclitaxel and carboplatin or China-approved bevacizumab in combination with paclitaxel and carboplatin for 4 to 6 cycles.
- Detailed Description
This is a randomized, double-blind, multinational, multicenter, active-control, parallel two-group Phase 3 clinical trial evaluating the efficacy and safety of TRS003 plus paclitaxel-carboplatin versus China-approved bevacizumab plus paclitaxel-carboplatin in patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. Approximately 608 subjects will be enrolled into this study from America, Europe and Asia. Patients who sign the informed consent and meet the inclusion criteria will be randomized (1:1) to receive either TRS003 or China-approved bevacizumab in combination with paclitaxel-carboplatin for 4 to 6 cycles. Patients will be stratified by region (Asia, Europe and America), gender, and cigarette smoking habit (previous smoker, smoker and non-smoker).
Patients will receive either TRS003 (Arm A), or China-approved bevacizumab (Arm B) first followed by the administration of paclitaxel and carboplatin. TRS003 or China-approved bevacizumab will be administered at 15 mg/kg by intravenous (IV) infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion (over 3 hours) Q3W on Day 1 of each cycle and carboplatin will be administered at an area under the plasma concentration-time curve (AUC) 6 mg/mL/ min (the maximum dose capped at 900 mg) by IV infusion (over 15 - 30 minutes) Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist.
Efficacy will be evaluated by the investigator per RECIST v1.1 (Eisenhauer et al., 2009). Efficacy evaluation will be performed at baseline and every 6 weeks ± 7 days during the 4-6 cycle combination treatment periods. After completion of combination treatments, efficacy evaluations will be performed every 9 weeks ± 7 days (if patients received maintenance therapy). The analysis of Investigator-determined objective response rate (ORR) (RECIST v1.1) will be based on information obtained prior to Week 19. Investigator-determined duration of response (DOR) and progression-free survival (PFS) will also be evaluated according to RECIST v1.1. Data on overall survival (OS) will be collected. Central radiology review will not be required. However, for the purpose of quality control, the Sponsor may elect to have some or all tumor assessments to be reviewed by an independent imaging vendor.
Safety will be evaluated throughout the study. Adverse events will be recorded from the time of informed consent. Safety will be assessed based on periodically physical examination findings, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, laboratory variables (hematology, coagulation tests, serum chemistries, urinalysis and pregnancy tests), and electrocardiogram (ECG) findings. Adverse events and laboratories will be graded according to National Cancer Institute (NCI) CTCAE v5.0.
Immunogenicity will be assessed in all patients who received at least one dose of TRS003 or China-approved bevacizumab. Samples will be assessed for the development of antidrug antibodies to either TRS003, or China-approved bevacizumab. Neutralizing antibodies (NAb) will assessed in samples that are antidrug antibody (ADA) positive. Trough pharmacokinetics (PK) samples will be collected and will be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 608
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TRS003 TRS003 TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion Q3W on Day 1 of each cycle，carboplatin will be administered at an AUC 6 mg/mL/ min by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist. China-approved Bevacizumab China-approved Bevacizumab China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion Q3W on Day 1 of each cycle and carboplatin will be administered at an AUC 6 mg/mL/min (the maximum dose capped at 900 mg) by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist. TRS003 Paclitaxel TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion Q3W on Day 1 of each cycle，carboplatin will be administered at an AUC 6 mg/mL/ min by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist. TRS003 Carboplatin TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion Q3W on Day 1 of each cycle，carboplatin will be administered at an AUC 6 mg/mL/ min by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist. China-approved Bevacizumab Carboplatin China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion Q3W on Day 1 of each cycle and carboplatin will be administered at an AUC 6 mg/mL/min (the maximum dose capped at 900 mg) by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist. China-approved Bevacizumab Paclitaxel China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m\^2 by IV infusion Q3W on Day 1 of each cycle and carboplatin will be administered at an AUC 6 mg/mL/min (the maximum dose capped at 900 mg) by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist.
- Primary Outcome Measures
Name Time Method ORR,Objective Response Rate 19 weeks Investigator-determined confirmed ORR by Week 19 per RECIST v1.1 will be determined in the intention-to-treat (ITT) population in each arm.
- Secondary Outcome Measures
Name Time Method PFS, Progression-free survival 19 weeks PFS is defined as the time from randomization to Investigator-determined progressive disease (PD) or death due to any cause in the absence of documented PD.
OS, Overall survival 19 weeks OS is defined as the time from randomization to death due to any cause and will be analyzed by Kaplan-Meier method.
DOR, Duration of response 19 weeks DOR is defined as the time from the date of the first documentation of Investigator-determined response in patients with confirmed objective tumor response (complete response or partial response) to the first documentation of Investigator determined disease progression (PD) or to death due to any cause in the absence of documented PD.
Number of Participants with Treatment-Related Adverse Events (AEs) 23 weeks AEs will be assigned to preferred term using MedDRA and graded according to CTCAE v5.0.
Number of Participants with Immunogenicity 23 weeks ADA will be assessed in all patients. NAb will be assessed in samples that are ADA positive
AUC0-inf, Area Under the Serum Concentration Versus Time Curve (Time 0 to Infinity) 23 weeks PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
AUC0-t, Area Under the Serum Concentration Versus Time Curve (Time 0 to t) 23 weeks PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
Cmax, Maximum Drug Concentration 23 weeks PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
Trial Locations
- Locations (11)
Beijing Hospital
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of Xingtai Medical College
🇨🇳Xingtai, Hebei, China
FAW General Hospital of Jilin Province
🇨🇳Changchun, Jilin, China
The Second Affiliated Hospital of Suzhou University
🇨🇳Suzhou, Jiangsu, China
Wuhan Fourth Hospital
🇨🇳Wuhan, Hubei, China
Nanchong Central Hospital
🇨🇳Nanchong, Sichuan, China
Anhui Provincial Center Hospital
🇨🇳Hefei, Anhui, China
Chinese Academy of Medical Sciences, Cancer Hospital
🇨🇳Beijing, Beijing, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Fifth People's Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China