Onvansertib in Combination With Gemcitabine and Nab-paclitaxel for the Treatment of Patients With Locally-advanced, Unresectable, or Metastatic Pancreatic Ductal Adenocarcinoma

PRIMARY OBJECTIVE: I. To assess preliminary response to treatment with onvansertib and gemcitabine and nab-paclitaxel (GnP). SECONDARY OBJECTIVES: I. To assess the safety of onvansertib in combination with GnP. II. To assess the rate of disease control following treatment with onvansertib and GnP in patients with PDAC. III. To estimate the duration of response (DOR). IV. To estimate the time to disease progression. V. To estimate the progression-free survival associated with onvansertib and GnP. VI. To estimate the overall survival associated with onvansertib and GnP. EXPLORATORY OBJECTIVE: I. To evaluate therapy induced changes in the tumor and tumor ecosystem. OUTLINE: This is a safety lead-in study of onvansertib in combination with GnP, followed by a phase II study. Patients are assigned to 1 of 2 groups. GROUP 1: Patients receive onvansertib orally (PO) once daily (QD) on days 1-5, 8-12, and 15-19 and gemcitabine intravenously (IV) and nab-paclitaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo electrocardiography at baseline, as well as blood sample collection, tumor biopsy, computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) throughout the trial. GROUP 2: Patients receive onvansertib PO QD on days 1-10. Patients then receive onvansertib, gemcitabine, and nab-paclitaxel as in Group 1. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo electrocardiography at baseline, as well as blood sample collection, tumor biopsy, CT, MRI, and/or PET throughout the trial. Upon completion of the study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months from date of last dose of study drug.