A Phase 2 Trial of SCO-101 in Combination With FOLFIRI for Patients With Metastatic Colorectal Cancer (mCRC) With Acquired Resistance to FOLFIRI

Inclusion Criteria: Subjects are required to meet all of the following criteria forenrollment into the applicable stage (stage 1, stage 2 or stage 3) of the study:

1. Ability to understand and willingness to provide written informed consent before anytrial-related activities.
2. Age 18 years or older.
3. Histologically verified colorectal adenocarcinoma.
4. Non-resectable mCRC in patients A. Stage 1 only: with or without known BRAF, KRAS orrepair enzyme mutations. B. Stage 2 and stage 3 only: without known BRAF, KRAS orrepair enzyme mutations
5. A. Stage 1 only: Documented progressive disease on FOLFIRI treatment regimen (with orwithout antiangiogenetic and EGFR inhibitory biological treatment). B. Stage 2 and stage 3 only: Documented progressive disease with a prior benefit (SDfor more than 16 weeks, or CR or PR) on FOLFIRI treatment regimen (with or withoutantiangiogenetic and EGFR inhibitory biological treatment).
6. Maximum reduction of 33% in prior dose of FOLFIRI.
7. No indication for treatment with an oxaliplatin-containing treatment regimen. Thepatient may have received oxaliplatin treatment after treatment with FOLFIRI.
8. A. Stage 1 only: Evaluable disease by CT scan or MRI. B. Stage 2 and stage 3 only:Measurable disease by CT scan or MRI, according to RECIST. 1.1.
9. Performance status of ECOG ≤ 1.
10. Recovered to Grade 1 or less from prior surgery or acute toxicities of priorradiotherapy or treatment with cytotoxic or biologic agents.
11. ≥ 2 weeks must have elapsed since any prior surgery.
12. Adequate conditions as evidenced by the following clinical laboratory values:

• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 6.0 mmol/L
• Platelets ≥ 100 x 109 /L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN*
• Total serum bilirubin ≤ 1.0 ULN**
• Alkaline phosphatase ≤ 2.5 x ULN*
• Creatinine ≤ 1.5 ULN
• eGFR within normal limits.
• Adequate blood clothing function as defined by the International Normalized Ratio (INR) ≤ 1.2;

13. Life expectancy equal to or longer than 3 months.
14. Sexually active males and females of child-producing potential must use highlyeffective contraception (intrauterine devices, hormonal contraceptives (contraceptivepills, implants, transdermal patches, hormonal vaginal devices or injections withprolonged release)) for the study duration and at least 6 months after the last doseof study drug.
15. Signed informed consent.

• AST is not mandatory. In case of known liver metastases with ALT and AST ≤ 5 xULN and/or alkaline phosphatase ≤ 5 x ULN: Patients who do not conform to thetransaminase and/or alkaline phosphatase inclusion criteria, but who by the PIare considered in good PS and otherwise eligible for inclusion, and where thetransaminase and/or alkaline phosphatase levels are considered elevated due toother reasons than deteriorated lever capacity, may be considered for inclusionbased on conferred agreement between PI and sponsor.
• Unconjugated bilirubin may be measured as the difference between totalbilirubin and conjugated bilirubin.

Exclusion Criteria: Subjects meeting any of the following criteria will be excluded fromenrollment:

1. Concurrent chemotherapy, radiotherapy, or other investigational drug exceptnon-disease related conditions (e.g. insulin for diabetes) during study period.
2. Malabsorption syndrome or previous surgeries with resection of the stomach or smallintestine, whereby absorption of SCO-101 may be affected. This includes patients withileostomy.
3. Difficulty in swallowing tablets.
4. Clinical symptoms of CNS metastases requiring steroids.
5. Any active infection requiring parenteral or oral antibiotic treatment.
6. Known HIV positivity.
7. Known active hepatitis B or C.
8. Clinical significant (i.e. active) cardiovascular disease:

• Stroke within ≤ 6 months prior to day 1
• Transient ischemic attach (TIA) within ≤ 6 months prior to day 1
• Myocardial infarction within ≤ 6 months prior to day 1
• Unstable angina
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF)
• Serious cardiac arrhythmia requiring medication

9. Mental status is not fit for clinical study or CNS disease including symptomaticepilepsy.
10. Other medications or conditions that in the Investigator's opinion wouldcontraindicate study participation of safety reasons or interfere with theinterpretation of study results. Other severe medical conditions, including seriousheart disease, unstable diabetes, uncontrolled hypercalcemia, clinically activeinfections or previous organ transplants. Participation in another clinical trial withexperimental medication within 30 days prior to registration.
11. Known hypersensitivity to irinotecan, 5-FU or capecitabine
12. Pregnant women or women who are breastfeeding.