NCT06557733

An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis

Phase 2 Study to Evaluate the Efficacy and Safety of TPST-1495 in Patients With Familial Adenomatous Polyposis (FAP)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This open-label phase II trial tests how well TPST-1495 works in reducing the number of polyps in the small bowel and colon in patients with familial adenomatous polyposis (FAP). FAP is an inherited condition in which numerous polyps (growths that protrude from mucous membranes) form on the inside walls of the colon and rectum. It increases the risk for colon cancer. TPST-1495 binds to specific prostaglandin receptors. TPST-1495 is a dual antagonist of the prostaglandin E2 (PGE2) receptor subtypes EP2 and EP4, while sparing the immune-stimulating EP1 and EP3 receptors. TPST-1495 may help reduce the number of polyps in the small bowel and colon in patients with FAP.

Detailed description

PRIMARY OBJECTIVES: I. To assess the activity of TPST-1495 in reducing duodenal polyp burden in patients with FAP. II. To assess the safety of TPST-1495 in patients with FAP; we will evaluate the incidence of grade 2 or 3 adverse events. SECONDARY OBJECTIVE: I. The activity of TPST-1495 in reducing rectum/IPAA (ileal pouch-anal anastomosis) polyp burden in patients with FAP. EXPLORATORY OBJECTIVES: I. Reduction in intestinal polyp burden as a function of immunohistochemical staining at baseline and end of intervention (6-months) of rectal and duodenal tissue samples for COX-2 expression level, beta-catenin, and Ki-67. II. Proteomic profile of serum correlated to clinical response to therapy compared between baseline and end of intervention. III. Biospecimen acquisition. OUTLINE: Patients receive TPST-1495 orally (PO) once daily (QD) for 6 months in the absence of unacceptable toxicity. Patients also undergo esophagogastroduodenoscopy (EGD) and gastrointestinal (GI) endoscopy with biopsy at baseline and end of treatment and undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up at 1 month.

Conditions

• Colorectal Carcinoma
• Familial Adenomatous Polyposis

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	EP2/EP4 Antagonist TPST-1495	Given PO
PROCEDURE	Esophagogastroduodenoscopy	Undergo EGD
PROCEDURE	Gastrointestinal Endoscopy	Undergo GI endoscopy
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2026-03-31
• Primary completion: 2027-06-30
• Completion: 2027-06-30
• First posted: 2024-08-16
• Last updated: 2026-04-13

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study