ACCENT: This phase study is trying to determine the effectiveness of administering a targeted therapy (AMP945), prior to chemotherapy (gemcitabine and nab-paclitaxel), in people with pancreatic cancerA Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination With Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients

Exclusion

1. Pregnant or breast-feeding, or plans to become pregnant during the study.
2. Has received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -8.
3. Known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no oedema, no steroids and stable in 2 scans at least 4 weeks apart).
4. Gastrointestinal condition that could interfere with the swallowing or absorption of study medication.
5. Part A: Has received prior systemic treatments for pancreatic cancer, except those given in the adjuvant setting, and with recurrence more than 6 months after completion of curative/adjuvant treatment.
6. Part B: Has received no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Participants having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
7. History of malignancy other than in situ cancer or basal or squamous cell skin cancer in the last 5 years.
8. Major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day -8.
9. Known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections or known to be positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C Antibody.
10. Known history of myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 6 months prior to the first dose of study drug.
11. Focal palliative radiotherapy (e.g., to a bony metastasis) within the 14 days prior to Run-in, or more extensive radiotherapy within 28 days prior to Run-in.
12. History of chronic leukemias (e.g., chronic lymphocytic leukemia).
13. History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
14. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
15. Clinical signs of active infection and/or a temperature of > 38.0°C at the time of Screening or Baseline. Study entry may be deferred at the discretion of the Principal Investigator (PI).
16. Currently using warfarin.
17. Administration of a live virus vaccine in the 4 weeks prior to Day -8 or plans to receive a live virus vaccine during the study.
18. Clinically significant allergies to AMP945, nab-paclitaxel or gemcitabine (or any of their excipients), including hypersensitivity reactions to human albumin, that are not likely to be well controlled with premedication or other supportive measures.
19. Exhibiting any of the conditions or events outlined in the Contraindications or Special Warnings and Precautions sections of the nab-paclitaxel and/or gemcitabine package inserts.
20. Peripheral neuropathy > Grade 1.
21. Corrected QT interval using Fridericia's correction (QTcF) > 460 ms for males and >480 ms for females.
22. Any clinically relevant medical, social, or psychiatric conditions, or any finding during Screening, which in the Investigator's opinion may put the participant at unacceptable risk or interfere with the study objectives.
23. Prior treatment with AMP945.