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

NCT04416035 | Unknown Phase 3 FDA Drug

• 1 other identifier: TRS00303001
• Study Type: interventional
• Target: 608
• Locations: 1 country
• Sites: 11

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.

Conditions

Advanced Non-squamous Non-small-cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• ORR,Objective Response Rate

  Investigator-determined confirmed ORR by Week 19 per RECIST v1.1 will be determined in the intention-to-treat (ITT) population in each arm.

  19 weeks

Secondary Outcomes (8)

• PFS, Progression-free survival

  19 weeks

• OS, Overall survival

  19 weeks

• DOR, Duration of response

  19 weeks

• Number of Participants with Treatment-Related Adverse Events (AEs)

  23 weeks

• Number of Participants with Immunogenicity

  23 weeks

Study Arms (2)

TRS003

EXPERIMENTAL

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.

Biological: TRS003; Drug: Carboplatin; Drug: Paclitaxel

China-approved Bevacizumab

ACTIVE COMPARATOR

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.

Biological: China-approved Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

Interventions

TRS003 BIOLOGICAL

TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Each cycle is 3 weeks.

TRS003

China-approved Bevacizumab BIOLOGICAL

China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W).Each cycle is 3 weeks.

China-approved Bevacizumab

Carboplatin DRUG

Carboplatin will be administered at an 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.

China-approved Bevacizumab; TRS003

Paclitaxel DRUG

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

China-approved Bevacizumab; TRS003

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) ≤ 3×ULN 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:

You may not qualify if:

• 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/μL.
• 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.

Sponsors & Collaborators

• Zhejiang Teruisi Pharmaceutical Inc.: lead

Study Sites (11)

Anhui Provincial Center Hospital

Hefei, Anhui, China

RECRUITING

Chinese Academy of Medical Sciences, Cancer Hospital

Beijing, Beijing Municipality, 100021, China

RECRUITING

Beijing Hospital

Beijing, Beijing Municipality, China

RECRUITING

The Second Affiliated Hospital of Xingtai Medical College

Xingtai, Hebei, China

RECRUITING

Wuhan Fourth Hospital

Wuhan, Hubei, China

RECRUITING

The Second Affiliated Hospital of Suzhou University

Suzhou, Jiangsu, China

RECRUITING

FAW General Hospital of Jilin Province

Changchun, Jilin, China

RECRUITING

Jinan Central Hospital

Jinan, Shandong, China

RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Shanghai Fifth People's Hospital, Fudan University

Shanghai, Shanghai Municipality, China

RECRUITING

Nanchong Central Hospital

Nanchong, Sichuan, China

RECRUITING

MeSH Terms

Interventions

Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Yuankai Shi, MD

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yilin Li

CONTACT

(+86)5722126820; yilin.li@teruisipharm.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 4, 2020
• Study Start: August 17, 2020
• Primary Completion: October 21, 2021
• Study Completion: November 10, 2021
• Last Updated: August 31, 2020

Record last verified: 2020-08

Locations

CN (11)