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
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Napabucasin; Paclitaxel
Intervention description: 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.; 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.
Intervention MeSH terms: Paclitaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoplasms; Neoplasms by Site; Lung Neoplasms; Thoracic Neoplasms; Respiratory Tract Neoplasms; Bronchial Neoplasms

Summary:

      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.
    

Eligibility criteria:

        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