Two-Part, Open-Label, Multi-Center, Phase 1/2 Study of BIW-8962 as Monotherapy in Subjects With Lung Cancer

Study Overview
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Brief Summary
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This Phase 1/2 study is designed to assess the following: safety and tolerability of BIW-8962, Dose Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D) in Phase 1 in subjects with advanced/recurrent lung cancers or mesothelioma and preliminary efficacy in Phase 2 in subjects with advanced/recurrent Small Cell Lung Cancer.

Official Title
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Two-Part, Open-Label, Multi-Center, Phase 1/2 Study of Anti-GM2 Ganglioside Monoclonal Antibody BIW-8962 as Monotherapy in Subjects With Previously Treated Advanced/Recurrent Lung Cancer or Mesothelioma

Conditions
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Phase 1 Portion : Non Small Cell Lung Cancer(NSCLC), Small Cell Lung Cancer(SCLC), Mesothelioma, Phase 2 Portion : Small Cell Lung Cancer(SCLC)

Intervention / Treatment
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* Drug: BIW-8962


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1: histopathological-documented, measurable or non-measurable unresectable, advanced primary or recurrent SCLC, NSCLC or mesothelioma Phase 2: measurable, unresectable advanced or recurrent SCLC A life expectancy > 3 months Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 at study entry Echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) ≥ 50%, or ≥ institution's established lower limit of normal Adequate hematologic, hepatic, renal and lung function Exclusion Criteria: Subject received cytotoxic anti-cancer chemotherapy, orally available signaling pathway-targeted therapy, hormonal therapy, radiotherapy, immunotherapy, or investigational agents within 3 weeks prior to the first dose Subject received monoclonal antibodies within 4 weeks of the first dose Major surgery within 4 weeks prior to the first dose Known symptomatic brain metastases Clinically significant cardiovascular disease Leptomeningeal disease Uncontrolled intercurrent illness including ongoing or active infection, uncontrolled diabetes, etc Known HIV disease or acquired immunodeficiency syndrome-related illness A psychiatric illness, disability or social situation Hypersensitivity reaction to monoclonal antibodies, other therapeutic proteins A history of primary brain/CNS malignancy Neurological paraneoplastic syndrome

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIW-8962<br>Phase 1 - Dose escalation based on the BIW-8962 tolerability and safety data obtained from three subjects enrolled in a cohort (first cycle of treatment), enrollment at the next dose level or additional subjects into the ongoing cohort will occur Phase 2 - Recommended dose determined in Phase 1 | Drug: BIW-8962<br>* Phase 1 -With a standard 3+3 dose escalation design, the enrollment in Phase 1 will proceed until the MTD has been defined or the highest dose level has been reached. BIW-8962 will be administered intravenously on day 1 of each 21 day cycle. Phase 2 - RP2D of BIW-8962 determined in phase 1 portion will be administered until progression or unacceptable toxicity develops.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - To determine Maximum Tolerated Dose(MTD) | Phase 1 -Adverse Event collection and assessment will be done for all potentially treated subjects to assess the safety, tolerability, and determine the DLTs, maximum tolerated dose (MTD). | First 3-week cycle of treatment | 
| Phase 2 - To assess the objective response rate(Partial Response and Complete Response) | Phase 2 - Tumor response and progression will be evaluated every 6 weeks using RECIST v 1.1. Partial Response (PR) or Complete Response (CR) will be confirmed 4 weeks after first detection of response. | Until Progressive Disease (PD) determined | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - To evaluate preliminary efficacy | Phase 1 - Tumor response progression will be evaluated using RECIST V1.1 for the assessment of efficacy | Until Progressive Disease (PD) determined | 
| Phase 1 - To determine the q3w pharmacokinetic profile of BIW-8962 | Phase 1 - Pharmacokinetic (PK) parameters such as Maximum concentration (Cmax), time to maximum concentration (Tmax), minimum concentration(Cmin), area under the curve (AUC), half-life (t1/2), clearance (CL), and etc., are assessed. | Pre-dose, and Day 1, 2, 3, 5, 8, 12 and 15 in Cycle 1 and 3, Pre-dose in Cycle 2, 4, 5,and up to Cycle 6 | 
| Phase 2 - To assess safety and tolerance | Phase 2 - All safety information will be collected and then evaluated. | Every 3 weeks, until 45days after the last dose or within 7 days prior to the initiation of subsequent anti-cancer treatment |