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

Inclusion Criteria: * Participant must provide written informed consent before any study-specific procedures or interventions are performed * Participants are \>= 18 years old at the time of informed consent. Both men and women of all races and ethnic groups will be included * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Histologically or cytologically-proven adenocarcinoma of the exocrine pancreas with locally advanced or metastatic disease * Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 * Must have at least one disease lesion that is amenable to biopsy procedures performed per institutional standards * Must have progressed on, been intolerant to, or refused systemic therapy that is consistent with institutional standards (e.g., Gemcitabine-based, or fluorouracil, irinotecan, leucovorin and oxaliplatin \[FOLFORINOX\]) * Must not have received any systemic therapy or other investigational agents within 30 days or 5 half-lives (whichever is longer) from first dose of study therapy \* This requirement is waived for patients receiving cobimetinib or other investigational agent(s) as part of participation in NCT04005690, provided that all prior study-drug-related toxicities pertaining to NCT04005690 have resolved to grade =\< 1 prior to initiating study intervention * Hemoglobin: \>= 8.5 g/dL with no blood transfusion within 14 days of starting treatment * White blood cells (WBC): \> 2.…