Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Participants With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Condition: Metastatic Pancreatic Ductal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Momelotinib; Placebo to match momelotinib; Nab-paclitaxel; Gemcitabine
Intervention description: Tablet (s) administered orally once or twice daily; Placebo to match momelotinib tablets administered orally once or twice daily; Intravenously administered over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle; Intravenously administered over approximately 30 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle
Intervention MeSH terms: Paclitaxel; Gemcitabine; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      There will be two phases to this study. The lead-in phase will evaluate the safety,
      pharmacokinetics, and define the maximum tolerated dose (MTD) of momelotinib (MMB) combined
      with nab-paclitaxel and gemcitabine (nab-P + G) in adults with previously untreated
      metastatic pancreatic ductal adenocarcinoma. The randomized treatment phase will evaluate the
      efficacy, safety, and tolerability of nab-P + G with either MMB administered at the MTD or
      placebo in adults with previously untreated metastatic pancreatic ductal adenocarcinoma.
      Participants will continue study treatment until disease progression, unacceptable toxicity,
      consent withdrawal, or participant's refusal of treatment. Following treatment, participants
      will be followed for safety for 30 days and for survival approximately every 3 months for up
      to 3 years.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

               -  Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR

               -  Pathologist confirmed histological/cytological diagnosis of adenocarcinoma
                  consistent with pancreas origin in conjunction with either:

                    -  The presence of a mass in the pancreas, OR

                    -  A history of resected pancreatic adenocarcinoma

          -  Measurable disease per RECIST v1.1

          -  Adequate organ function defined as follows:

               -  Total bilirubin ≤ 1.25 x upper limit of the normal range (ULN); aspartate
                  transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN

               -  Absolute neutrophil count (ANC) > 1500 cells/mm^3, platelet > 100,000 cells/mm^3,
                  hemoglobin > 9 g/dL

               -  Serum creatinine < ULN OR calculated creatinine clearance (CrCl) of ≥ 60 ml/min

          -  Eastern Cooperative Oncology Group (ECOG ) 0 or 1

          -  Modified Glasgow prognostic score (mGPS) of 1 or 2 at Screening (randomized phase
             only)

        Key Exclusion Criteria:

          -  Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy for pancreatic
             adenocarcinoma

          -  Currently or previously treated with biologic, small molecule, immunotherapy,
             chemotherapy, or other agents for metastatic pancreatic carcinoma

          -  Major surgery within 28 days of first dose of study drug

          -  Minor surgical procedure(s) within 7 days of enrollment or not yet recovered from
             prior minor surgery (placement of central venous access device, fine needle
             aspiration, or endoscopic biliary stent ≥ 1 day before enrollment is acceptable)

          -  Known positive status for HIV

          -  Chronic active or acute viral hepatitis A, B, or C infection (testing required for
             hepatitis B and C), or hepatitis B or C carrier

          -  Peripheral neuropathy ≥ Grade 2

          -  Known or suspected brain or central nervous system metastases

          -  Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma,
             adenocarcinoma originating from the biliary tree or cystadenocarcinoma

          -  History of interstitial pneumonitis and/or require supplemental oxygen therapy

          -  External biliary drain

          -  Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6
             months of enrollment

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.