tailOred dRug repurposIng of dEcitabine in KRAS-dependeNt refracTory pAncreaTic cancEr

Inclusion Criteria:

1. Age ≥ 18 years;
2. Histologically or cytologically proven, advanced, inoperable (metastatic or locally advanced), PDAC;
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
4. Life expectancy of at least 12 weeks;
5. At least one and no more than two lines of systemic treatment for advanced disease;
6. At least one metastatic lesion(s) and/or primary tumor amenable to pre-treatment biopsy;
7. KRAS dependency, as assessed by molecular analysis of RNA isolated from a fresh tumor biopsy;
8. Imaging-documented progressive disease (PD), according to modified RECIST 1.1 criteria;
9. Imaging-documented measurable disease, according to modified RECIST 1.1 criteria;
10. Adequate organ and marrow function;
11. Postmenopausal status or evidence of non-childbearing status (negative urine or serum pregnancy test) for women of childbearing potential;
12. Women of childbearing potential (defined as not post- menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use two highly effective forms of contraception while they are receiving

Exclusion Criteria:

1. Uncontrolled intercurrent illness(es);
2. Pregnancy or lactation;
3. Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy;
4. Major surgical intervention within 4 weeks prior to enrollment;
5. Radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to signing the treatment ICF;
6. Any previous treatment with DEC;
7. Patients with second primary cancers, except for adequately treated non- melanoma skin cancer, curatively treated in-situ cancer of the cervix, stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) treated with curative intent and with no evidence of active disease at \>1 year from the completion of curative treatment prior to study entry;
8. Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia;
9. Serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug;
10. Serious psychiatric or medical conditions that could interfere with a valid informed consent.