MYL-1402O Compared With Avastin®, in Patients With Stage IV nsNSCLC

MYL-1402O is a monoclonal antibody currently being developed by Mylan GmbH, as a proposed biosimilar to European Union and US licensed Avastin (hereafter referred to as Avastin), which is approved as first line treatment in combination with carboplatin and paclitaxel (CP) for patients with Stage IV unresectable, recurrent or metastatic nsNSCLC. This randomized equivalence study is designed to meet the global regulatory requirement for approval of a biosimilar product. For this study, both MYL-1402O and Avastin are considered investigational medicinal products (IMP).

• Bevacizumab as MYL-1402O (Biological): Bevacizumab as MYL-1402O 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV
• Bevacizumab as Avastin (Biological): Bevacizumab as Avastin 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV

Primary outcomes

• Primary Efficacy Analysis of Overall Response Rate ( ORR) of MYL-1402O as Compared to Avastin [18 weeks after first dosing per patient]: The primary efficacy endpoint Overall Response Rate (ORR) will be based on best tumor responses as assessed by an independent review at any time point during the first 18 weeks, and assessed according to RECIST 1.1. The primary efficacy analysis is based on the ratio of the MYL-1402O ORR to the Avastin ORR at Week 18 based on the Intent to Treat ( ITT) set of patients.

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

1. Written and signed informed consent
2. Male or female at least 18 years of age with documented imaging diagnosis of Stage IV unresectable, recurrent or metastatic nsNSCLC with at least one measurable lesion as defined by RECIST 1.1
3. Documented histologic or cytologic diagnosis of advanced nsNSCLC with negative or unknown sensitizing epidermal growth factor receptor (EGFR) mutation, and negative or unknown echinoderm microtubule-associated protein like 4 anaplastic lymphoma kinase (EML4 ALK) rearrangement.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
5. Has not received any prior systemic therapy for first-line treatment of advanced lung cancer, except adjuvant chemotherapy, and remained disease-free for at least 12 months from time of surgery, and at least 6 months from last dose of chemotherapy.
6. Treated and stable brain metastasis.

Key Exclusion Criteria:

1. Documented squamous NSCLC or small cell type or large cell neuroendocrine histology
2. History of significant hemoptysis, central tumors with proximity to large vessels and tumor with cavitation
3. Received prior treatment with paclitaxel, bevacizumab or anthracycline or had known hypersensitivity to any of these components.
4. Recent significant cardiac condition or vascular event or inadequately controlled hypertension.
5. On anticoagulant therapy not considered stable
6. Risk of hemorrhage in the central nervous system
7. Recent history of surgery, nonhealing wound, active ulcer, or untreated bone fracture.
8. History of gastrointestinal fistula, perforation, or abscess.

Participant flow

Outcome results

• Primary Efficacy Analysis of Overall Response Rate ( ORR) of MYL-1402O as Compared to Avastin (Primary), Count of participants, Participants: MYL-1402O 140; Avastin 144

Adverse events

Time frame: Active collection period of AEs will be from the time the patient signs the ICF through the Safety Follow Up Visit. Pre-existing diseases or conditions (reported at time of screening) will not be considered AEs unless there is an increase in the frequency or severity, or a change in the quality of the disease or condition. Progression of NSCLC and its consequences will not be collected as an AE even if they lead to hospitalization or meet any other seriousness criteria including death.

Serious adverse events by term

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Other adverse events by term

2 more sites not listed.

• Study Protocol (PDF, 2019-02-19)
• Statistical Analysis Plan (PDF, 2019-08-21)

• Tazeen A Idris, MD, Study director