An open-label phase 1b/2 study assessing the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma

Prior treatment

• Has received attenuated vaccine within 28 days before the first dose of study treatment
• Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab
• Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has received prior treatment with irinotecan or platinum-containing chemotherapy
• Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)

Other illness

• Any condition that, in the opinion of the Investigator, would place the patient at increased risk or preclude the patient’s compliance with the study
• Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has known Gilbert's disease
• Has other current cancer or history of cancer in the prior 3 years before signing the ICF other than in situ cervical cancer, or basal cell or squamous cell carcinoma treated with local excision only
• Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment: Has a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity, pneumonitis or multiple allergies
• Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment: Has a history of Peripheral Artery Disease (eg, claudication, Leo Buerger's disease)
• Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment: Has a history of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)
• Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
• Has a history of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
• Has uncontrolled intercurrent illness, including active infection
• Has a known history of HIV, hepatitis B or active hepatitis C infection

Lab values

• Has QTc >450 msec

Other

• Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
• Is a female patient who is pregnant or nursing
• Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has pre-existing peripheral neuropathy greater than grade 1
• Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has known genotype UGT1A1 * 28 / * 28
• Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has known fructose intolerance (malabsorption)
• Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has complete dihydropyrimidine dehydrogenase (DPD) deficiency
• Has known CNS metastases or carcinomatous meningitis

• Has provided written informed consent
• Has acceptable clinical chemistry laboratory values defined as: a. Bilirubin ≤1.5 x ULN (biliary drainage is permitted) b. AST ≤3 x ULN (irrespective of hepatic metastases) c. ALT ≤3 x ULN (irrespective of hepatic metastases) d. Creatinine ≤1.5 x ULN or glomerular filtration rate (GFR) of ≥45 mL/min (see APPENDIX 4 for calculation of GFR) e. INR ≤1.5 x ULN f. Albumin ≥28 g/L
• For women of childbearing potential: a. Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at screening b. Is willing to use highly effective contraception methods (defined in APPENDIX 5) during study treatment and for at least six months thereafter
• Fertile men must practice effective contraceptive methods (i.e. surgical sterilization, or a condom used with a spermicide) during study treatment and for at least six months thereafter
• Is willing to comply with all study procedures
• Is ≥18 years of age at the time of signing the informed consent form (ICF)
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)
• Has measurable disease per RECIST v. 1.1
• Has not received previous chemotherapy for pancreatic ductal adenocarcinoma
• Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target lesions)
• Has a life expectancy of ≥ 3 months
• Has acceptable hematologic laboratory values defined as: a. Neutrophils ≥ 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test b. Platelets ≥100 x 109/L c. Hemoglobin ≥6.2 mmol/L (~100 g/L) (may be after transfusion)