A Study to Compare the Similarity in Efficacy and Safety Between TRS003 and China-approved Bevacizumab in NSCLC

  • STATUS
    Recruiting
  • End date
    Nov 10, 2021
  • participants needed
    608
  • sponsor
    Zhejiang Teruisi Pharmaceutical Inc.
Updated on 25 January 2021

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.

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.

Details
Condition Advanced Non Squamous Non Small Cell Lung Cancer
Treatment carboplatin, Paclitaxel, TRS003, China-approved Bevacizumab
Clinical Study IdentifierNCT04416035
SponsorZhejiang Teruisi Pharmaceutical Inc.
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Advanced Non Squamous Non Small Cell Lung Cancer?
Do you have any of these conditions: Do you have Advanced Non Squamous Non Small Cell Lung Cancer??
Male or female 18 years
Signed and dated informed consent form
Willing and able to comply with all study procedures
Histologically or cytologically confirmed unresectable, locally advanced, recurrent, or metastatic nonsquamous NSCLC; if the tumor shows multiple histologies, the main cellular phenotype will be used. Must provide archived tumor tissue obtained within 3 years for epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) testing. If archival tissue meeting this requirement is not available, patients will undergo biopsy to be eligible for study entry
No previous systemic therapy targeting the primary tumor or sites of metastases. Adjuvant therapy should be completed at least 6 months prior to study entry. Patients may have received radiation therapy if this was completed at least 1 month prior to entry and if other sites of measurable disease (per RECIST v11) are present
At least one measurable lesion per RECIST v1.1
ECOG performance status score 0 or 1
Life expectancy 6months
Adequate hepatic function as evidence by meeting all the following requirements
Total bilirubin 1.5 upper limit of normal (ULN)
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) 3ULN or ALT 5 ULN if liver metastases are present
Adequate renal function as evidence by meeting all the following requirements
Serum creatinine 1.5 ULN and calculated creatinine clearance (CrCL) > 50 mL/min (Cockroft-Gault Equation) or estimated glomerular filtration rate (GFR) > 50 mL/min
Urine dipstick for proteinuria < 2+. If urine dipstick is greater than or equal to 2+, proteinuria must be less than 2 g in 24 hours or the urine protein/creatinine ratio < 2\
Hematological function defined as
Platelet count 100,000/l without transfusion within 2 weeks prior to the study screening
Prothrombin time, international normalized ratio or activated partial thromboplastin time < 1.5 ULN
Absolute neutrophil count 1,500/l without any medical interventional treatment within two weeks prior to the study screening (ie, granulocyte-colony stimulating factors and/or herbal remedies)
Hemoglobin (Hb) 9 g/dl without the need for transfusion within 2 weeks prior to the study screening

Exclusion Criteria

Known sensitizing EGFR mutations or ALK rearrangements
Squamous lung cancer, mixed small cell and non-small cell lung cancer or squamous cell-dominant adeno-squamous lung cancer
Tumor cavitation, invading into large blood vessels or close to large vessels (such as pulmonary artery or Superior vena cava
Significant thrombotic or hemorrhagic events within 6 months prior to the study screening e.g., hemoptysis > 2.5 mL of red blood, gastrointestinal bleeding, hematemesis, central nervous system hemorrhage, severe epistaxis or vaginal bleeding, etc
Severe cardiovascular disease, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction and significant vascular disease (including but not limited to aneurysm requiring surgical repair or recent artery thrombosis); unstable angina pectoris, New York Heart Association (NYHA) class III or IV heart failure and uncontrollable arrhythmia within 6 months prior to entry
History of active gastroduodenal ulcer, abdominal fistula as well as non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to the study screening
Central nervous system (CNS) metastases; Subjects with asymptomatic CNS metastases who are neurologically stable 4 weeks following CNS-directed therapy with no evidence of CNS disease progression 4 weeks, and on a stable or decreasing dose of corticosteroids may be eligible and should be discussed with the Medical Monitor
Concurrent malignancy within 5 years other than adequately treated primary cervical cancer, skin-squamous or basal cell carcinomas, prostatic cancer following radical resection that does not require therapy, prostate cancer treated with active surveillance, ductal carcinoma in situ of the breast, or < T1 urothelial carcinoma
Uncontrolled hypertension (systolic blood pressure >150 mmHg and diastolic blood pressure >100 mmHg at the study screening), or a history of hypertension crisis or hypertensive encephalophy
Active hepatitis B or hepatitis C virus. Patients with evidence of infection with hepatitis B who have an undetectable viral load are eligible for study entry. Patients with evidence of infection with hepatitis C should have completed curative therapy
Known to be positive for human immunodeficiency virus (HIV) and with an AIDS defining opportunistic infection within 12 months of study entry or a CD4 T cell count < 359 cells/L
Full dose anticoagulants, including oral or parenteral; Low dose anti-coagulation (not intended to achieve a therapeutic INR) for port patency is permitted. No Factor Xa inhibitors. No aspirin or other nonsteroidal anti-inflammatory drugs that can inhibit platelet within ten days prior to screening. No history of hemorrhagic or thrombotic disorders (e.g., hemophilia, protein C deficiency)
Thoracic radiotherapy within 4 weeks prior to screening or palliative radiotherapy for metastasis outside thoracic region within 2 weeks prior to screening
Any major surgical procedure within 28 days prior to screening or anticipated elective surgery during the study. Any minor surgery such as deep vein catheterization within 48 hours prior to the first dose of the study drugs
Evidence of pericardial or pleural effusion or ascites that requires intervention
Treatment history of monoclonal antibodies or small molecule inhibitors against vascular endothelial growth factor (VEGF) or its receptor (VEGFR), including bevacizumab
Clinically uncontrolled active infection requiring systemic therapy within 2 weeks prior to entry
Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products
Participation in any other clinical trial within 4 weeks prior to screening. Recipient of any anticancer therapy (other than hormones used to treat breast cancer) within 4 weeks prior to screening
Women of childbearing potential who are pregnant or is breast feeding or who do not consent to use highly effective methods of birth control during treatment and for an additional 120 days after the last administration of the protocol specified treatment
Men with a partner of childbearing potential who does not consent to use highly effective methods of birth control during treatment and for an additional 120 days after the last administration of the protocol specified treatment
Any condition that the Investigator or primary physician believes may not be appropriate for participating the study
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note