Phase 1b/2 study to assess the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.

OPTIMIZE-1 is a phase 1b/2, open-label, multi-center study assessing the clinical efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.

The efficacy of intravenously administered mitazalimab in combination with the standard of care chemotherapy mFOLFIRINOX will be evaluated in patients with metastatic pancreatic ductal adenocarcinoma. Two dose levels of mitazalimab, 450 ug/kg and 900 ug/kg, are planned to be evaluated together with mFOLFIRINOX for determination of recommended phase 2 dose (RP2D) of mitazalimab in combination with mFOLFIRINOX before entering a dose expansion part with RP2D obtained. The expansion part will evaluate the clinical efficacy of mitazalimab in combination with mFOLFIRINOX assessing objective response rate (ORR), primary endpoint, as well as Progression-free survival (PFS) and Overall survival (OS). The dose expansion part includes a Simon´s two-stage design with an interim analysis for stop for futility or efficacy based on ORR.

Inclusion Criteria:

1. Has provided written informed consent

2. Is ≥18 years of age at the time of signing the informed consent form (ICF)

3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)

5. Has measurable disease per RECIST v. 1.1

6. Has not received previous chemotherapy for pancreatic ductal adenocarcinoma

7. Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target lesions)

8. Has a life expectancy of ≥ 3 months

9. Has acceptable hematologic laboratory values defined as:

   1. Neutrophils ≥ 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test
   2. Platelets ≥100 x 109/L
   3. Hemoglobin ≥6.2 mmol/L (~100 g/L) (may be after transfusion)

10. Has acceptable clinical chemistry laboratory values defined as:

    1. Bilirubin ≤1.5 x ULN (biliary drainage is permitted)
    2. AST ≤3 x ULN (irrespective of hepatic metastases)
    3. ALT ≤3 x ULN (irrespective of hepatic metastases)
    4. Creatinine ≤1.5 x ULN or glomerular filtration rate (GFR) of ≥45 mL/min
    5. INR ≤1.5 x ULN
    6. Albumin ≥28 g/L

11. For women of childbearing potential1:

    1. Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at screening
    2. Is willing to use highly effective contraception methods during study treatment and for at least six months thereafter

12. 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

13. Is willing to comply with all study procedures

Exclusion Criteria:

1. Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
2. 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
3. Has known CNS metastases or carcinomatous meningitis
4. Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)
5. Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
6. 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
7. Has QTc >450 msec
8. Has uncontrolled intercurrent illness, including active infection
9. Has a known history of HIV, hepatitis B or active hepatitis C infection
10. Is a female patient who is pregnant or nursing
11. Has received attenuated vaccine within 28 days before the first dose of study treatment
12. 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
13. Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab
14. Has received prior treatment with irinotecan or platinum-containing chemotherapy
15. Has pre-existing peripheral neuropathy greater than grade 1
16. Has known Gilbert's disease
17. Has known genotype UGT1A1 * 28 / * 28
18. Has known fructose intolerance (malabsorption)
19. Has complete dihydropyrimidine dehydrogenase (DPD) deficiency