This study is testing narmafotinib, a type of drug called a focal adhesion kinase (FAK) inhibitor, when it is given in combination with 4 chemotherapy drugs in a regimen called FOLFIRINOX, to patients who have pancreatic cancer which has metastasised (spread). The study is being run in 2 parts.

Part A will test increasing dose levels of narmafotinib in at least 3 people per dose at up to 4 dose levels to assess safety.

Part B will test 2 of the dose levels from Part A in 20 people per dose, to select the best dose to take forward into future studies.

Participants will take narmafotinib as oral capsules every day. They will also receive mFOLFIRINOX chemotherapy on Day 1 and and Day 15 of 28-day cycles.

Inclusion Criteria:

• Aged at least 18 years at the time of consent.
• Confirmed diagnosis of metastatic pancreatic adenocarcinoma (PDAC) within the 6 weeks prior to study start and have not received treatment for metastatic PDAC.
• Have measurable disease by RECIST v1.1.
• Eligible for treatment with mFOLFIRINOX as standard of care therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Have a life expectancy of > 3 months.
• Adequate organ function
• Agree to use effective contraception.

Exclusion Criteria:

• Pregnant or breast-feeding
• Have received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -7.
• Neuroendocrine or acinar cell pancreas tumors.
• Known brain metastases.
• Conditions that could interfere with the swallowing or absorption of study medication.
• Received previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
• Received cytotoxic doses of any 5-FU based chemotherapy.
• Any chemotherapy related toxicities greater than grade 1 from prior neoadjuvant or adjuvant therapy for PDAC.
• Human immunodeficiency virus (HIV) infection and/or history of Hepatitis B infection or known to have active hepatitis B or C.
• Uncontrolled angina, myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 1-year prior to the first dose of study drug.
• History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis.
• Clinical signs of active infection at the time of Screening or Baseline.
• Clinically significant allergies to narmafotinib, mFOLFIRINOX components (or any of their excipients) that are not likely to be well controlled with pre-medication or other supportive measures.
• Any of the conditions or events outlined in the Contraindications or Special Warnings and Precautions sections of the mFOLFIRINOX component package inserts.
• Peripheral neuropathy > Grade 1.
• Prior treatment with narmafotinib or other FAK inhibitor within the 2 years prior to screening.