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

Study Overview
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Brief Summary
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The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-06439535 (CN) in combination with paclitaxel and carboplatin versus bevacizimab 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.

Official Title
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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

Conditions
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Advanced Non-squamous NSCLC

Intervention / Treatment
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* Drug: PF-06439535 (CN)
* Drug: Bevacizumab-EU
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>PF-06439535 (CN) + paclitaxel + carboplatin | Drug: PF-06439535 (CN)<br>* 15 mg/kg, IV on day 1 of each 21 day cycle for up to 2 years, or until progression or unacceptable toxicity develops.<br>Drug: Paclitaxel<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>|
| Active Comparator: Arm B<br>Bevacizumab-EU + paclitaxel + carboplatin | Drug: Bevacizumab-EU<br>* 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<br>* Other names: Avastin;Drug: Paclitaxel<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Objective Response Rate (ORR) by Week 19 | 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 (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. | 25 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Safety characterized by type, incidence, severity, timing, seriousness, and relationship to investigational product of adverse events, including cardiotoxicity and infusion related reactions, and laboratory abnormalities | From time of ICD signed to 2 years | 
| Serum Concentration of Bevacizumab |  | up to 2 years | 
| Number of Participants With Anti-Drug Antibody (ADA) |  | up to 2 years | 
| Number of Participants With Neutralizing Antibody (NAb) | Only samples that were confirmed positive for ADA were further tested for NAb. | up to 2 years |