Clinical Trials

Inclusion Criteria:

1. Male or female and ≥ 18 years of age.

2. Have provided written informed consent to participate in the study.

3. Diagnosis of phenotypic classical FAP with disease involvement of the duodenum or the
residual colon/rectum/pouch as the primary disease site.

4. Genetic diagnosis of FAP with APC gene mutation (Part 2 only).

5. Has undergone colectomy or subtotal colectomy.

6. No significant cardiovascular abnormalities.

7. No significant hematopoietic abnormalities.

8. No significant hepatic abnormalities.

9. No significant renal abnormalities.

10. Female participants must have a negative serum pregnancy test prior to Study Day 1.

11. All participants must be willing to follow the contraceptive guidance in the protocol.

12. Absence of gross blood in stool at Screening.

13. Participant must be willing to discontinue use of non-steroidal anti-inflammatory
agents (NSAIDs) prior to Study Day 1.

Exclusion Criteria:

1. No clinically significant laboratory abnormality, medical or psychiatric illness.

2. Has had prior pelvic irradiation.

3. Has gastrointestinal disease or recent gastrointestinal procedure that could interfere
with oral absorption of REC-4881.

4. Has received treatment with other investigational agents prior to Study Day 1.

5. Treatment with other FAP-directed drug therapy within 8 weeks of screening endoscopy
(Part 2 only).

6. Is currently under treatment for desmoid tumors.

7. Use of omega-3 fatty acids or oral corticosteroids prior to Study Day 1.

8. Use of strong CYP3A inhibitors or inducers prior to Study Day 1.

9. History of an ongoing or newly diagnosed eye abnormality.

10. Cancer on biopsy at screening endoscopy in GI tract (including stomach, duodenum, and
colon/rectum/pouch) (Part 2 only).

11. Has a large polyp (>1 cm) not amenable to complete removal.

12. Has active pancreatitis secondary to pancreatic duct obstruction.

13. Has active gall bladder disease.

14. Is pregnant, lactating or is planning to attempt to become pregnant during the study.

15. Has had major surgery prior to Study Day 1.

16. Has an active infection requiring systemic therapy.

17. Has known hypersensitivity to the study drug or its excipients.

18. History of alcohol or substance abuse.

19. Received treatment with another MEK inhibitor prior to Screening.

20. Active or known HIV, hepatitis B or hepatitis C infections.

21. Has a severe or uncontrolled medical condition.

22. Use of strong BCRP or MRP2 inhibitors prior to Study Day 1.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/18/23.  Questions regarding updates should be directed to the study team contact.