A Study of Napabucasin (BBI-608) Plus Weekly Paclitaxel Versus Weekly Paclitaxel Alone in Patients With Advanced, Previously Treated, Non-Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is an international, multi-center, prospective, randomized, open-label Phase 3 clinical trial of the cancer stemness inhibitor napabucasin administered with weekly paclitaxel versus weekly paclitaxel alone in patients with advanced non-squamous non-small cell lung cancer who have disease progression following systemic treatment with a platinum-based combination regimen in the metastatic setting, who have received treatment with an immune checkpoint inhibitor if a candidate, additional approved therapies, and for whom weekly paclitaxel is an acceptable treatment option.

Official Title
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A Phase III Randomized, Open-Label Clinical Trial of BBI-608 Plus Weekly Paclitaxel Versus Weekly Paclitaxel Alone in Patients With Advanced, Previously Treated, Non-Squamous Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Napabucasin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have histologically or cytologically confirmed non-squamous NSCLC. Must have progressed following treatment with platinum-based combination chemotherapy for metastatic disease, and patients with an EGFR or ALK/ROS1 genetic aberration must have received appropriately targeted treatment. Must have received either nivolumab or pembrolizumab or a different IND-approved anti-PD1 or anti-PD-L1 therapy, unless medically contraindicated Weekly paclitaxel must be an acceptable treatment option Must submit tumor tissue for correlative analyses Women of child-bearing potential and partners of women of child-bearing potential must take measures to avoid pregnancy while receiving and for a period of time following protocol therapy Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function, and a life expectancy of ≥ 3 months Key Exclusion Criteria: Has squamous NSCLC Has received prior systemic treatment with a taxane for advanced/metastatic disease Has received systemic anti-cancer therapy within the 14 days prior to randomization Has received radiotherapy within the 28 days prior to randomization, with the exception of palliative radiotherapy to focal lesions for pain or other symptom control Has brain metastases with evolving neurologic symptoms or a steroid requirement. Has had major surgery requiring general anesthesia and/or mechanical ventilation within the 28 days prior to randomization Has a corrected QT interval (QTc) > 470 ms or has an electrocardiogram (ECG) with a new abnormal finding that is clinically significant Has peripheral neuropathy ≥ Grade 2 (NCI-CTCAE) Refuses to complete quality of life questionnaires either alone or with assistance from study staff despite adequate fluency Has an intercurrent (non-malignant) chronic medical or psychiatric illness or condition(s) not optimally controlled and carrying a moderate to high risk of interfering with protocol therapy administration or compliance with required procedures, in the judgment of the investigator

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Napabucasin plus Weekly Paclitaxel<br>Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with paclitaxel administered intravenously, once weekly, on 3 of every 4 weeks. | Drug: Napabucasin<br>* Napabucasin will be administered in continuous 28-day cycles. The starting dose of napabucasin is 240 mg twice daily (480 mg total daily dose) with approximately 12 hours between each dose. Napabucasin should be taken with fluids either 1 hour prior to a meal or 2 hours after a meal.<br>* Other names: BB608;Drug: Paclitaxel<br>* Paclitaxel will be administered intravenously, once weekly, via one-hour infusion at a starting dose-level of 80 mg/m^2 body surface area. The weekly paclitaxel infusion will be given during 3 out of every 4 weeks, on days 1, 8, and 15 of each 28-day study cycle.<br>|
| Active Comparator: Weekly Paclitaxel<br>Patients randomized to this arm will receive weekly paclitaxel alone administered intravenously, once weekly, on 3 of every 4 weeks. | Drug: Paclitaxel<br>* Paclitaxel will be administered intravenously, once weekly, via one-hour infusion at a starting dose-level of 80 mg/m^2 body surface area. The weekly paclitaxel infusion will be given during 3 out of every 4 weeks, on days 1, 8, and 15 of each 28-day study cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Overall Survival of patients with previously treated advanced, non-squamous non-small cell lung cancer. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival in Biomarker Positive Patients | To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Overall Survival of patients with previously treated advanced, non-squamous non-small cell lung cancer in biomarker positive patients. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue. | 36 months | 
| Progression Free Survival | To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Progression Free Survival (PFS) of patients with previously treated advanced, non-squamous non-small cell lung cancer. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. | 36 months | 
| Progression Free Survival in Biomarker Positive Patients | To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Progression Free Survival (PFS) of patients with previously treated advanced, non-squamous non-small cell lung cancer in biomarker positive patients. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue. | 36 months | 
| Disease Control Rate in Biomarker Positive Patients | To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Disease Control Rate (DCR) of patients with previously treated advanced, non-squamous non-small cell lung cancer. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue. | 36 months | 
| Quality of Life (QoL) | QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) in patients with previously treated advanced, non-squamous non-small cell lung cancer with napabucasin plus weekly paclitaxel versus weekly paclitaxel. | 36 months | 
| Disease Control Rate | To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Disease Control Rate (DCR) of patients with previously treated advanced, non-squamous non-small cell lung cancer. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. | 36 months | 
| Number of Patients With Adverse Events | All patients who have received at least one dose of napabucasin will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasms, Neoplasms by Site, Lung Neoplasms, Thoracic Neoplasms, Respiratory Tract Neoplasms, Bronchial Neoplasms