A BRIDGING STUDY OF PF-06439535 (CN) PLUS PACLITAXEL-CARBOPLATIN VERSUS BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN IN NSCLC

A RANDOMIZED, DOUBLE-BLIND BRIDGING SAFETY AND EFFICACY STUDY OF PF-06439535 (CN) PLUS PACLITAXEL-CARBOPLATIN VERSUS BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN FOR THE FIRST-LINE TREATMENT OF CHINESE PARTICIPANTS WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER

The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-06439535 (CN) in combination with paclitaxel and carboplatin versus bevacizumab sourced from the European Union (bevacizumab-EU) with paclitaxel and carboplatin in Chinese participants with advanced non-squamous NSCLC in the first-line treatment setting.

Study Overview

• Status: Terminated
• Conditions: Advanced Non-squamous NSCLC
• Intervention / Treatment: Drug: PF-06439535 (CN); Drug: Paclitaxel; Drug: Carboplatin; Drug: Bevacizumab-EU

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Dongguan, Guangdong, China, 523059
      • Dongguan People's Hospital
  • Hebei
    • Baoding, Hebei, China, 071000
      • Affiliated Hospital of Hebei University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female participants age at least 18 years of age.
• Newly diagnosed Stage IIIB, IIIC or IV non small cell lung cancer (NSCLC) (according to American Joint Committee on Cancer (AJCC) Staging Manual, 8th Edition, last updated 05 June 2018) or recurrent NSCLC.
• Histologically or cytologically confirmed diagnosis of non-squamous NSCLC.
• At least one measurable lesion as defined by RECIST v1.1.
• Be eligible to receive 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.
• Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that, in the opinion of the investigator, is likely to bleed.
• Known EGFR activating mutations (for example, exon 19 deletion or exon 21 L858R substitution mutations) or ALK rearrangements.
• Prior systemic therapy for advanced NSCLC; prior neoadjuvant or adjuvant therapy is allowed if surgical resection for primary disease was performed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; PF-06439535 (CN) + paclitaxel + carboplatin	Drug: PF-06439535 (CN); 15 mg/kg, IV on day 1 of each 21 day cycle for up to 2 years, or until progression or unacceptable toxicity develops.; Drug: Paclitaxel; 175 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; AUC 5 (max=750mg) 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.
Active Comparator: Arm B; Bevacizumab-EU + paclitaxel + carboplatin	Drug: Paclitaxel; 175 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; AUC 5 (max=750mg) 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: Bevacizumab-EU; 15 mg/kg, IV on day 1 of each 21 day cycle until disease progression, unacceptable toxicity or 25 weeks. At Week 25, the participants with clinical benefit will received PF-06439535 (CN) monotherapy for up to 2 years from randomization in this study; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Objective Response	Objective response referred to 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 (non-progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions, normal nodes (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.	From Week 1 to Week 25 (25 Weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period	TEAE was defined as any adverse event that occurs after the beginning of the investigational product or any pre-existing adverse event (AE) that worsens after the beginning of the investigational product. Serious adverse events (SAE) were assessed by the investigator. Severity of AE was graded based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3-SEVERE AE; Grade 4-LIFE-THREATENING consequences; urgent intervention indicated; Grade 5-DEATH RELATED TO AE.	From Day 1 to end of Cycle 8; 1 Cycle = 21 Days
Number of Participants With Anti-Drug Antibodies (ADA)	ADA have been evaluated in studies with bevacizumab in cancer patient populations. A sensitive and specific immunoassay for detecting ADA in human serum was used to analyze the ADA samples (blood samples for assessment of ADA collected at specified timepoints).	Pre-dose on Day 1 of Cycle 1 and Cycle 5, and before the last administration of the investigational product (up to Cycle 14 Day 1); 1 Cycle = 21 Days
Number of Participants With NAb	Blood samples for assessment of ADA and NAb were collected at specified time point. Samples that were determined positive for ADA were further characterized for NAb using a single validated NAb assay.	Pre-dose on Day 1 of Cycle 1 and Cycle 5, and before the last administration of the investigational product (up to Cycle 14 Day 1); 1 Cycle = 21 Days
Trough and Apparent Peak PF-06439535 (CN) and Bevacizumab (EU) Concentrations	The drug concentrations were determined using serum samples collected at the time points specified.	Pre-dose on Day 1 of Cycle 1 and Cycle 5, and before the last administration of the investigational product (up to Cycle 14 Day 1); 2.5 hours after initiation of bevacizumab infusion on Day 1 of Cycle 1 and Cycle 5; 1 Cycle = 21 Days
Number of Participants With TEAEs in Extension Period	Treatment emergent adverse event (TEAE) was defined as any adverse event that occurs after the beginning of the investigational product or any pre-existing adverse event that worsens after the beginning of the investigational product. Serious adverse events were assessed by the investigator. Severity of AE was graded based on NCI CTCAE version 4.03: Grade 3-SEVERE AE; Grade 4-LIFE-THREATENING consequences; urgent intervention indicated; Grade 5-DEATH RELATED TO AE.	Cycle 9 Day 1 up to End of Treatment (up to Cycle 14 Day 21); 1 Cycle = 21 Days

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2020
• Primary Completion (Actual): May 10, 2021
• Study Completion (Actual): May 10, 2021

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: March 26, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: B7391007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No