A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous NSCLC

• ClinicalTrials.gov Identifier: NCT02364999
• Recruitment Status: Completed
• First Posted: February 18, 2015
• Results First Posted: June 27, 2018
• Last Update Posted: February 7, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 10, 2015
• First Posted Date: February 18, 2015
• Results First Submitted Date: May 7, 2018
• Results First Posted Date: June 27, 2018
• Last Update Posted Date: February 7, 2019
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 31, 2018)

Objective Response Rate (ORR) by Week 19 [ Time Frame: 25 weeks ]

ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.

Original Primary Outcome Measures (submitted: February 10, 2015)

Best confirmed objective Response Rate (ORR) [ Time Frame: Week 19 ]

Comparison of the best confirmed objective response rate (ORR) by Week 19 in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC

Current Secondary Outcome Measures (submitted: December 4, 2018)

• Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: 55 weeks ]
  AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
• Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) [ Time Frame: 55 weeks ]
  Laboratory evaluation included hematology (hemoglobin, white blood cells, platelets and absolute neutrophil count), blood chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, serum or plasma creatinine, sodium, potassium, total calcium, magnesium, blood urea nitrogen or urea, and albumin ), coagulation (international normalized ratio for prothrombin time and activated partial thromboplastin time) and urinalysis (dipstick followed by a quantitative urine protein analysis for results of 2+ or greater).
• Duration of Response (DOR) [ Time Frame: 55 weeks ]
  DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. DOR was based on the Brookmeyer and Crowley method.
• Progression Free Survival Rate at 55 Weeks [ Time Frame: 55 weeks ]
  This outcome measure refers to the possibility of being progression free at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.
• Survival Rate at 55 Weeks [ Time Frame: 55 weeks ]
  This outcome measure refers to the possibility of being alive at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.
• Serum Concentration of Bevacizumab up to 1 Year [ Time Frame: Pre-dose from Cycle 1 to Cycle 17, 2.5 hours post-dose in Cycle 1, and 1.5 hours post-dose in Cycle 5 ]
• Number of Participants With Anti-Drug Antibody (ADA) [ Time Frame: 55 weeks ]
  ADA assay was performed using a sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) method, which used biotinylated- and ruthenium-labeled PF-06439535 as reagents. Samples with ADA titer greater than or equal to (>=) 2.29 were considered positive.
• Number of Participants With Neutralizing Antibody (NAb) [ Time Frame: 55 weeks ]
  Only samples that were confirmed positive for ADA were further tested for NAb. The NAb analysis was conducted using a single validated quasi-quantitative enzyme-linked immunosorbent assay (ELISA) that utilized PF-06439535 as a reagent. Samples with NAb titer >=1.70 were considered positive.

Original Secondary Outcome Measures (submitted: February 10, 2015)

• Duration of response (DOR) [ Time Frame: 12 months ]
  Duration of response (DOR)
• Peak and trough [ Time Frame: 12 months ]
  Peak and trough bevacizumab-Pfizer concentrations at selected cycles
• Incidence of anti-drug (bevacizumab) antibodies (ADA), including neutralizing antibodies (NAb) [ Time Frame: 12 months ]
  Incidence of anti-drug (bevacizumab) antibodies (ADA), including neutralizing antibodies (NAb)
• Progression-free survival [ Time Frame: 12 months ]
  1 year progression-free survival (PFS) rate
• Survival Rate [ Time Frame: 12 months ]
  1-year survival rate
• Peak and trough [ Time Frame: 12 months ]
  Peak and trough bevacizumab-EU concentrations at selected cycles

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous NSCLC
• Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF- 06439535 PLUS PACLITAXEL-CARBOPLATIN AND BEVACIZUMAB PLUS PACLITAXEL -CARBOPLATIN FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER.
• Brief Summary: This is a multinational, double-blind, randomized, parallel-group Phase 3 clinical trial evaluating the efficacy and safety of bevacizumab-Pfizer plus paclitaxel and carboplatin versus bevacizumab-EU plus paclitaxel and carboplatin in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Bevacizumab-Pfizer
  Bevacizumab-Pfizer: 15 mg/kg IV on Day 1 of a 21-day cycle for each of at least 4 and no more than six (6) 21-day cycles, followed by the assigned blinded bevacizumab monotherapy.
• Drug: Bevacizumab-EU
  bevacizumab-EU: 15 mg/kg IV on Day 1 of a 21-day cycle for each of at least 4 and no more than six (6) 21-day cycles followed by the assigned blinded bevacizumab monotherapy.
• Drug: Paclitaxel
  Paclitaxel 200 mg/m2 via IV infusions on Day 1 of a 21-day cycle for each of at least 4 and no more than six (6) 21-day cycles.
• Drug: Carboplatin
  carboplatin AUC =6.0 via IV infusions on Day 1 of a 21-day cyclefor each of at least 4 and no more than six (6) 21-day cycles.

Study Arms

• Experimental: Bevacizumab-Pfizer
  Bevacizumab-Pfizer plus paclitaxel and carboplatin
  Interventions:

  • Drug: Bevacizumab-Pfizer
  • Drug: Paclitaxel
  • Drug: Carboplatin
• Active Comparator: Bevacizumab-EU
  Bevacizumab-EU plus paclitaxel and carboplatin
  Interventions:

  • Drug: Bevacizumab-EU
  • Drug: Paclitaxel
  • Drug: Carboplatin

Publications *

• Li CSW, Sweeney K, Cronenberger C. Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin(R)) in patients with advanced non-squamous non-small cell lung cancer. Cancer Chemother Pharmacol. 2020 Mar;85(3):487-499. doi: 10.1007/s00280-019-03946-8. Epub 2019 Nov 26.
• Reinmuth N, Bryl M, Bondarenko I, Syrigos K, Vladimirov V, Zereu M, Bair AH, Hilton F, Liau K, Kasahara K. PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin(R)), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study. BioDrugs. 2019 Oct;33(5):555-570. doi: 10.1007/s40259-019-00363-4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 17, 2017): 719
• Original Estimated Enrollment (submitted: February 10, 2015): 798
• Actual Study Completion Date: December 2017
• Actual Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female patients age at least 18 years of age, or age of consent in the region.
• Newly diagnosed Stage IIIB or IV non-small cell lung cancer (according to Revised International System for Staging Lung Cancer criteria of 2010) or recurrent non-small cell lung cancer (NSCLC).
• Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC.
• Be eligible to receive study treatment of bevacizumab, paclitaxel, and carboplatin based on local standard of care, for the treatment of advanced or metastatic non-squamous NSCLC.

Exclusion Criteria:

• Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature.
• Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that is likely to bleed.
• Known sensitizing EGFR mutations (for example, deletion 19 or L858R) or EML4-ALK translocation positive mutations.
• Prior systemic therapy for NSCLC; prior neoadjuvant or adjuvant therapy is allowed if surgical resection for primary disease was performed.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Bulgaria, Chile, Croatia, Czechia, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Philippines, Poland, Romania, Russian Federation, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United States
• Removed Location Countries: Czech Republic, Hong Kong, Slovakia

Administrative Information

• NCT Number: NCT02364999
• Other Study ID Numbers: B7391003; 2014-003878-16 ( EudraCT Number ); B7391003 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: January 2019