Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of calaspargase pegol-mknl in combination with cobimetinib. SECONDARY OBJECTIVES: I. To assess the safety of calaspargase pegol-mknl in combination with cobimetinib. II. To assess preliminary response to treatment with calaspargase pegol-mknl and cobimetinib. III. To monitor levels of plasma asparaginase. EXPLORATORY OBJECTIVE: I. To evaluate therapy induced changes in the tumor and tumor ecosystem. OUTLINE: This is a dose-escalation study. Patients receive calaspargase pegol-mknl intravenously (IV) over 1 hour on day 1 and cobimetinib orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo a biopsy before cycle 1, day1 and again on cycle 2 day 15 per the investiagator's discretion, with an additional biopsy at the time of disease progression. After completion of study intervention, patients are followed up at 3 and 6 months.