Efficacy and Safety of QL1101 and Avastin® Respectively Combined With Paclitaxel and Carboplatin in the First-line Treatment of Non-squamous Non-small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT03169335
• Recruitment Status: Completed
• First Posted: May 30, 2017
• Last Update Posted: August 24, 2018
• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Qilu Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: May 23, 2017
• First Posted Date: May 30, 2017
• Last Update Posted Date: August 24, 2018
• Actual Study Start Date: March 28, 2017
• Actual Primary Completion Date: June 23, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2017)

Objective response rate [ Time Frame: 18 weeks ]

The actual endpoint is best response seen during the study

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 25, 2017)

• Disease control rate [ Time Frame: 3 months, 6 months, 9 months, 1 year ]
  DOR is defined as the time from the first tumor evaluation as CR or PR to the first evaluation as PD or death
• Overall survival (OS) [ Time Frame: 18 months after enrollment and randomization of the last case ]
  OS is defined as the time from randomization and grouping to patient death due to various causes. For patients who are lost to follow-up, the date when they were contacted for the last time will be used as the cut off time.
• Progression-free survival (PFS) [ Time Frame: 18 months after enrollment and randomization of the last case ]
  PFS is defined as the time from randomization and grouping to PD or death.
• Treatment-emergent adverse events [ Time Frame: 18 weeks ]
  Assessment following therapy with either QL1101 or avastin

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of QL1101 and Avastin® Respectively Combined With Paclitaxel and Carboplatin in the First-line Treatment of Non-squamous Non-small Cell Lung Cancer
• Official Title: A Multi-center, Randomized, Double-blind, Parallel, Two-group Phase III Clinical Study of the Efficacy and Safety of QL1101 and Avastin® Respectively Combined With Paclitaxel and Carboplatin in the First-line Treatment of Non-squamous Non-small Cell Lung Cancer
• Brief Summary: The objective of this study is to assess the similarity between QL1101 and Avastin® respectively combined with chemotherapy in terms of efficacy and safety in patients with non-squamous non-small cell lung cancer. The study intends to include first-line patients with non-squamous non-small cell lung cancer, and uses QL1101 combined with basic chemotherapy CP (paclitaxel + carboplatin). The regimen is consistent with the usage and dosage of Avastin® at home and abroad indicated for the treatment of non-squamous non-small cell lung cancer.
• Detailed Description: The study is a randomized, double-blind, positive drug-controlled, multi-center Phase III study. It is planned to enroll 512 treatment-naïve patients with non-squamous non-small cell lung cancer (NSCLC). Subjects are randomized into the QL1101 combined with paclitaxel/carboplatin or Avastin® combined with paclitaxel/carboplatin treatment group by a ratio of 1:1, and stratified by age (≥65 years, <65 years), sex (male, female) and EGFR subtype (sensitive mutation type, wild type).
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-squamous Non-small Cell Lung Cancer

Intervention

• Drug: QL1101
  targeted vascular endothelial growth factor (VEGF) monoclonal antibodies
• Drug: Avastin®
  targeted vascular endothelial growth factor (VEGF) monoclonal antibodies
  Other Name: bevacizumab
• Drug: Paclitaxel
  175 mg/m2, IV (in the vein) following investigational product on day 1 of each 21 day cycle. Number of cycles 4-6.
• Drug: Carboplatin
  AUC 5 IV, (in the vein) following paclitaxel on day 1 of each 21 day cycle. Number of cycles: 4-6.

Study Arms

• Experimental: Experimental group
  QL1101 + paclitaxel/carboplatin:subjects are given 15 mg/kg QL1101 on Day 1 of each cycle with every 3 weeks as a cycle, respectively combined with paclitaxel/carboplatin for 6 cycles (at least 4 cycles).
  Interventions:

  • Drug: QL1101
  • Drug: Paclitaxel
  • Drug: Carboplatin
• Active Comparator: Control group
  Avastin® + paclitaxel/carboplatin:subjects are given 15 mg/kg Avastin® on Day 1 of each cycle with every 3 weeks as a cycle, respectively combined with paclitaxel/carboplatin for 6 cycles (at least 4 cycles).
  Interventions:

  • Drug: Avastin®
  • Drug: Paclitaxel
  • Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 22, 2018): 535
• Original Estimated Enrollment (submitted: May 25, 2017): 512
• Actual Study Completion Date: July 13, 2018
• Actual Primary Completion Date: June 23, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged ≥18 years and ≤75 years; 2) Patients with histologically or cytologically confirmed inoperable locally advanced (Stage IIIb, not suitable for multidisciplinary treatment), metastatic (Stage IV), or relapsed non-squamous cell non-small cell lung cancer. Diagnostic result of non-squamous cell non-small cell lung cancer obtained based on sputum cytology should be immunohistochemically confirmed. If a variety of tumor ingredients are mixed, the main cell types should be classified;
• ECOG score of 0-1 points;
• At least one measurable lesion can be evaluated according to RECIST1.1 criteria; Lesions situated in a previously irradiated area are considered measurable only if marked progressive signs occur after irradiation
• Patients who have not received systemic anti-tumor therapy of locally advanced or metastatic non-squamous non-small cell lung cancer (if the subject received adjuvant therapy after completing the radical treatment of early non-small cell lung cancer, but then the disease relapsed, the subject can be enrolled. In this case, the end time of the adjuvant therapy is required to be more than 6 months from the time of the first administration of this study, and various toxic reactions resulting from the adjuvant therapy should have recovered (≤ Grade 1 by CTCAE 4.03 criteria, except for alopecia).
• Expected survival time ≥24 weeks.
• Subjects must give informed consent to this study prior to the trial and voluntarily sign a written informed consent form.

Exclusion Criteria:

• Central squamous cell carcinoma, and mixed gland squamous cell carcinoma with squamous cell as the main ingredient;
• ALK fusion gene is known to be positive;
• Medical history or examination shows thrombotic disease within 6 months prior to screening;
• Imaging shows signs of tumor invasion of large vessels, and the investigator or radiologist must exclude patients whose tumor has been completely close to or surrounded or invaded the lumen of large vessels (e.g., the superior pulmonary artery or superior vena cava);
• Patients with a past history of symptomatic brain metastases or meningeal metastases, or spinal cord compression;
• Patients who received palliative radiotherapy for bone lesions outside the chest within 2 weeks prior to the first dose of the study drug;
• Patients who received major surgical procedures (including thoracotomy), or suffered from major trauma (such as fractures) within 28 days prior to screening, or need to undergo major surgery during the expected study treatment period;
• Patients who received a minor surgical procedure within 48 hours prior to the first treatment with Anivitis®/QL1101 (the investigator judges whether there is bleeding tendency);
• Patients who are currently using or have recently used (within 10 days prior to the first dose of Avastin®/QL1101) aspirin (>325 mg/day) or other nonsteroidal antiinflammatory drugs known to inhibit platelet function, or full-dose anticoagulants;
• Patients whose medical history or examination shows hereditary bleeding tendency or coagulation disorders, which may increase the risk of bleeding; -Uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg);
• Patients who had a past history of hypertensive crisis or hypertensive encephalopathy;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03169335
• Other Study ID Numbers: QL1101-002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Qilu Pharmaceutical Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Qilu Pharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Qilu Pharmaceutical Co., Ltd.
• Verification Date: May 2017