TAB008 Compared to Avastin® in Patients With EGFR Wild-type Non-squamous Non-small Cell Lung Cancer

• Status: Completed
• Trial end date: 2020-03-24
• Target enrollment: 0
• Participant gender: All

Summary

In this randomized, double-blind, multicenter, phase III similarity study, treatment naive, EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (ns-NSCLC) patients were enrolled and randomized (1:1) into TAB008 or Bevacizumab-EU groups. Patients received TAB008 or bevacizumab-EU 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or bevacizumab-EU 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady state pharmacokinetics.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TOT Biopharm Co., Ltd.
• Treatments: Bevacizumab

Criteria

Inclusion Criteria:

1. Patients voluntarily participate in the study and sign the informed consent form;

2. Aged 18 to 75 years (inclusive), male or female;

3. Patients with histologically and/or cytologically confirmed, inoperable, locally advanced (Stage IIIb, IIIc), metastatic (Stage IV), or relapsed or progressive non-squamous cell carcinoma after local therapy (in cases of multiple tumor components, the predominant cell type is classified);

4. No sensitive mutation of epidermal growth factor receptor (EGFR) gene (18, 19, 21), no other known activating mutations (such as ALK, ROS) which has treatment approved by NMPA;

5. At least one measurable lesion according to RECIST 1.1 criteria; and this lesion has not received radiotherapy:

6. Definition of measurable disease: Lesions that can be precisely measured in at least one dimension by any of the following: computed tomography (CT) scan or magnetic resonance imaging (MRI) scan with enhanced spiral CT or multidetector CT (MDCT) with extra-nodal lesions at least 10 mm in diameter and lymph node lesions at least 15 mm in short axis when the slice thickness is 5 mm or less；

7. Patients who have never received systemic chemotherapy, anti-angiogenic drug and molecular targeted drug therapy for primary tumor or metastasis (note: subjects who received adjuvant therapy previously are allowed, but only patients who have no progression or recurrence during and within 6 months after completion of adjuvant therapy)；

8. 0 ≤ ECOG PS ≤ 1;

9. Expected survival time ≥ 3 months;

10. The subject has recovered from the damage caused by other local treatments, including radiotherapy or surgery > 4 weeks from the start of study treatment, and the wound has completely healed; however, patients who receive palliative radiotherapy for bone metastases 2 weeks before the start of study treatment can be allowed;

11. Laboratory tests within 14 days before randomization meet the requirements.

Exclusion Criteria:

1. Patients with brain metastases ;

2. History of bleeding diathesis, high risk of bleeding, or coagulopathy, including thrombotic disease within 6 months prior to Screening and/or hemoptysis (≥ 2.5 mL in a single cough) within 3 months prior to Screening;

3. CT/MRI image shows tumor encasement or invasion into the lumen of great vessels (e.g., pulmonary artery or superior vena cava) and patients with bleeding risk judged by the investigator;

4. Uncontrolled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg after combination therapy with two or more antihypertensive agents), and patients with a previous history of hypertensive crisis or hypertensive brain;

5. Significant cardiovascular or cerebrovascular disease;

6. Active peptic ulcer or fracture, active infection at randomization, tracheoesophageal fistula, gastrointestinal perforation or gastrointestinal fistula, and intra-abdominal abscess within 6 months before screening;

7. Patients who have undergone major surgical procedures (including open-heart biopsy), have major trauma, or are expected to require major surgery during the study;

8. Minor surgical procedures (e.g., deep veins, ports) within 24 hours prior to receiving study drug;

9. Moderate to large amount of pericardial effusion, abdominal or pleural effusion that cannot be controlled by pumping or other symptomatic treatment (symptomatic treatment is allowed, but drugs with anti-tumor indications such as chemotherapeutic drugs, anti-angiogenic drugs and molecular targeted drugs cannot be given);

10. Known hypersensitivity to bevacizumab, paclitaxel and carboplatin injection and its excipients;

11. Patients with other malignant tumors except lung cancer within 5 years;

12. Patients who have used other clinical study treatment within 4 weeks before the start of study treatment;

13. History of alcohol or drug abuse;

14. Pregnant and lactating women; women of childbearing potential and male patients who require effective contraceptive methods during the study and for 6 months after administration of study drug;

15. Other conditions that, in the opinion of the investigator, should not be included.