Clinical Trial to Investigate Safety, Tolerability and MTD for SCO-101 in Combination With Gemcitabine and Nab-paclitaxel in Inoperable Pancreatic Cancer Patients.

An Open-label Phase Ib Prospective Clinical Trial to Investigate Safety, Tolerability and Maximum Tolerated Dose for SCO-101 in Combination With Gemcitabine and Nab-paclitaxel in Inoperable Pancreatic Cancer Patients.

An open-label dose escalating phase Ib study of SCO-101 in combination with gemcitabine and nab-paclitaxel. The primary objectives are to establish the safety profile and the MTD of SCO-101 when combined with gemcitabine and nab-paclitaxel. The starting dose of SCO-101 is 150 mg and the dose may be increased to a maximum of 350 mg.

The study is an open-label dose escalating phase Ib study of SCO-101 in combination with gemcitabine and nab-paclitaxel. The primary objective is to establish the safety, tolerability and MTD of SCO-101 when combined with gemcitabine and nab-paclitaxel. Secondary objectives are efficacy and to establish PK parameters of SCO-101. The target indication is patients with inoperal pancreatic cancer who are to be treated with gemcitabine and nab-paclitaxel. The study is designed as a standard 3+3 dose escalation study with increasing doses of SCO-101 and a fixed dose (standard regimen) of gemcitabine and nab-paclitaxel. An interim report will be prepared once the last patient in the MTD cohort has completed one treatment cycle. Patients will continue treatment until disease progression to evaluate secondary objectives. One treatment Cycle is 28 days. The starting dose of SCO-101 is 150 mg 6 daily dosing in a bi-weekly schedule) and may be increased to a maximum of 350 mg (5 cohorts with 50 mg increments). A total of up to 18 patients are anticipated if dose escalation to the 5th cohort. Gemcitabine and nab-paclitaxel is administered according to local standard recommendations once weekly for three weeks followed by one weeks treatment holiday (dosing on day 6, day 13 and day 20). Patients may continue treatment until treatment progression.

Inclusion Criteria:

Patients are required to meet all of the following criteria for enrollment into the study:

1. Ability to understand and willingness to provide written informed consent before any trial-related activities.

2. Age 18 years or older.

3. Histologically or cytologically verified pancreatic adenocarcinoma.

4. Inoperable localized, locally advanced or metastatic pancreatic cancer, not amenable for curatively intended treatment, in patients who are to be treated with gemcitabine and nab-paclitaxel.

5. Measurable or non-measurable disease determined by CT scan or MRI, according to RECIST 1.1.

6. Performance status of ECOG ≤ 2 and expected to tolerate the standard recommended (100%) gemcitabine and nab-paclitaxel dose.

7. Recovered to Grade 1 or less from prior surgery or acute toxicities of prior radiotherapy or treatment with cytotoxic or biologic agents.

8. ≥ 2 weeks must have elapsed since any prior surgery or radiotherapy.

9. 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) ≤ 2.5 x ULN 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

10. Life expectancy longer than 3 months.

11. Sexually active males and females of child-producing potential must use highly effective contraception (intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) for the study duration and at least 6 months after the last dose of study drug.

12. Signed informed consent. *AST is not mandatory. In case of known liver metastases with ALT and AST ≤ 5 x ULN and/or alkaline phosphatase ≤ 5 x ULN: Patients who do not conform to the transaminase and/or alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase and/or alkaline phosphatase levels are considered elevated due to other reasons than deteriorated lever capacity, may be considered for inclusion based on conferred agreement between PI and sponsor.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from enrollment:

1. Concurrent chemotherapy, radiotherapy, or other investigational drug during study period.

2. Previous surgeries with resection of the complete stomach or greater part of small intestines (excluding the duodenum), whereby absorption of SCO-101 may be affected. Treatment with Creon or similar is allowed.

3. Difficulty in swallowing tablets.

4. CNS metastases requiring steroids.

5. Treatment with antibiotics for infections or with clinical symptoms of active infection. Patients showing symptoms of CoViD19 must be tested for active CoViD19 infection.

6. Known HIV positivity.

7. Known active hepatitis B or C.

8. Clinically significant (i.e. active) cardiovascular disease:

   • Stroke, Transient ischemic attack (TIA) or myocardial infarction within ≤ 6 months prior to day 1.
   • Unstable angina or NYHA Grade II or greater congestive heart failure (CHF).
   • Serious cardiac arrhythmia requiring medication.

9. Mental status, symptomatic epilepsy or other CNS disease where the investigator assesses the patient not fit for the clinical study.

10. Other medications or conditions that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results. Other severe medical conditions, including serious heart disease, unstable diabetes, uncontrolled hypercalcemia or previous organ transplants. Participation in another clinical trial with experimental medication within 30 days prior to registration.

11. Known hypersensitivity to gemcitabine and/or nab-paclitaxel.

12. Pregnant women or women who are breastfeeding.

13. Prior or present neuropathy > grade I (NCI-CTCAE v.5.0).

14. Curatively intended treatment.