Pilot Window of Opportunity Trial (POET)

Study Overview
=================
Brief Summary
-----------------
The proposed clinical trial with TPST-1495 can help people with two types of cancer, Endometrial Cancer (EC) and Colorectal Carcinoma (CRC), who need surgery. The investigator plans to evaluate how well TPST-1495 works against these cancers by checking blood samples and tumor tissues taken before and after the treatment to see if it is an effective treatment option to help the immune system fight against cancer.

Detailed Description
-----------------
TPST-1495, a dual antagonist targeting human prostaglandin E2 receptor subtypes EP2 and EP4, has shown promising safety and possesses potential immunomodulatory and antineoplastic properties in preclinical research. Based on previous clinical research, the investigator proposes that TPST-1495 treatment could offer anti-cancer benefits to endometrial cancer (EC) and colorectal cancer (CRC) patients. This pilot window-of-opportunity study aims to assess the safety and biological effectiveness of administering 50mg TPST-1495 orally once daily for seven days, with discontinuation three days prior to surgical therapy, involving 10 evaluable patients, with five each from the EC and CRC groups, for a maximum total of 20 participants enrolled to ensure 10 evaluable patients.

Official Title
-----------------
A Phase 2 Pilot Window of Opportunity Study of the EP2 and EP4 Receptors Inhibitor TPST-1495 in Patients With Endometrial Cancer or Colorectal Cancer Planning to Undergo Surgical Therapy

Conditions
-----------------
Colorectal Carcinoma (CRC), Endometrial Carcinoma (EC)

Intervention / Treatment
-----------------
* Drug: TPST-1495


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent signed and dated by the patient prior to the performance of any study-specific procedures, sampling, or analyses. At least 18 years of age at the time of signature of the informed consent form (ICF) Histologically confirmed endometrial cancer or colorectal cancer Must be candidates for surgical therapy. Male or female patients. Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. Male patients must also refrain from donating sperm during their participation in the study. To have archival tumor tissue specimen available. Otherwise, patients should agree to have tumor biopsy to obtain sufficient tissue for histological assessment. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 or 1. Life expectancy estimated to be > 12 weeks. Adequate organ and marrow function as defined per protocol. Exclusion Criteria: Concurrent enrollment in another clinical study, unless it is an observational clinical study, a specimen-collection study, or the follow-up period of an interventional study. Patients who used NSAID or COX-2 inhibitors across 4 days within 2 weeks prior to study treatment initiation. Patients with past medical history (PMH) of allergy or hypersensitivity, GI bleed, or ulceration secondary to NSAID's or COX-2 inhibitors. PMH of GI ulcer within one year of treatment initiation or history of untreated helicobacter's pylori infection. Subjects with history of treated helicobacter's pylori infection with confirmation of eradication are eligible. PMH of diverticulitis or any GI bleed within 2 years of treatment initiation. Heart failure classified by New York Heart Association as Classification II, III or IV. Active autoimmune disease or inflammatory disorders including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease) requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids, or immunosuppressive drug) within 2 years prior to treatment initiation. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations including a history of substance abuse that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. Subjects who are receiving anticoagulant therapy or considered to be at increased risk of bleeding (i.e., bleeding disorder or coagulopathy). Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This pilot window of opportunity study proposes to evaluate the safety and biological efficacy of 50mg TPST-1495 in patients with EC or CRC undergoing surgical therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pilot window of opportunity trial of TPST-1495<br> | Drug: TPST-1495<br>* Eligible subjects will receive study treatment of 50mg TPST-1495 taken orally, once a day for 7 days prior and discontinued 3 days prior to scheduled surgery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EP2 and EP4 receptor subtypes blood biomarker expression within the PGE2 signaling pathway. | Blood samples from patients with EC and/or CRC will be assessed at screening(pre-dose) and post-surgery to evaluate the expression of EP2 and EP4 receptor biomarkers within the PGE2 signaling pathway, providing insights into impact of TPST-1495 on pharmacodynamic pathway changes. | 1 years | 
| EP2 and EP4 receptor subtypes tumor biomarker expression within the PGE2 signaling pathway. | Tumor samples from patient with EC and/or CRC will be assessed at screening (pre-dose) and post-surgery to evaluate the expression of EP2 and EP4 receptor biomarkers within the PGE2 signaling pathway, providing insights into impact of TPST-1495 on pharmacodynamic pathway changes. | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor Activity | Number and percentage of participants with EC and/or CRC will be reported for anti-tumor activity of TPST-1495's, based on the measurement involving mean or median values of circulatory immune cells in blood samples and tumor tissues at screening(pre-dose) and post-surgery. | 2 years | 
| Biological Efficacy | Number and percentage of participants with EC and/or CRC will be assessed for biological efficacy of TPST-1495's, based on the measurement involving mean or median values of circulatory immune cells in blood samples and tumor tissues at screening (pre-dose) and post-surgery. | 2 years | 
| Rate of dynamic changes in immune cells | This measure involves comparing the mean or median values of pre-blood and post-blood samples to assess the dynamic changes in immune cell populations. Flow cytometry will be utilized to examine alterations in immune cell composition following treatment. | 2 years | 
| Rate of dynamic Changes in Inflammatory Cytokines and Chemokines | This outcome measure focuses on comparing the mean or median values of pre-blood and post-blood samples to evaluate dynamic changes in inflammatory cytokines and chemokines. Flow cytometry will be employed to assess variations in the levels of these important biomolecules in response to treatment. | 2 years | 
| Incidences of TPST-1495 drug therapy based potential adverse events | It utilizes CTCAE v5.0 to systematically report and assess the incidence and the severity of potential adverse events that patients may experience during treatment, ensuring consistent and reliable safety assessment. | 2 years |