RECRUITING

A First-In-Human, Phase 1 Study Evaluating Oral TACC3 PPI Inhibitor, AO-252, in Advanced Solid Tumors

Conditions

Triple Negative Breast Cancer High Grade Serous Ovarian Cancer Endometrial Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to assess the safety, tolerability and efficacy of the study drug AO-252 and identify the best dose for use in future studies.

Official Title

A First-In-Human, Phase 1 Study Evaluating Oral TACC3 PPI Inhibitor, AO-252, in Advanced Solid Tumors

Quick Facts

Study Start:2023-11-02

Study Completion:2027-01-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06136884

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Adults ≥ 18 years of age. Patient has TNBC; OR platinum-resistant HGSOC, primary peritoneal cancer, and/or fallopian-tube cancer; OR serous endometrial cancer, as described below. 2. TNBC: 1. Histologically or cytologically confirmed metastatic or locally recurrent unresectable TNBC per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria. 2. TNBC must have TP53 mutation/loss and be relapsed/refractory to at least 1 line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or be intolerant of existing therapy(ies). Prior exposure to an immune checkpoint inhibitor is allowed. 3. Platinum-resistant HGSOC, primary peritoneal cancer, and/or fallopian-tube cancer: 1. Histologically or cytologically confirmed diagnosis of metastatic or unresectable HGSOC, with TP53 mutation/loss, with platinum resistance defined as progression during or within 6 months of a platinum containing regimen, with no other standard treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed. 2. Patients whose tumors have progressed after at least 1 line of therapy for advanced/metastatic settings. 3. Systemic therapy with a PARP inhibitor will be counted as 1 line of therapy. Induction followed by maintenance will be counted as 1 line of therapy. 4. Serous endometrial cancer: 5. Measurable disease per RECIST v1.1 6. Adequate bone marrow reserve, cardiac, liver, and renal function: 7. Female patients of child-bearing potential must have a negative serum pregnancy test and use at least 1 form of acceptable birth control method listed below as approved by the Investigator before initiating study treatment and for 3 months after the last dose of study drug. 1. Sterilization 2. Any hormonal contraceptives (non-CYP 3A4 inhibitors) associated with inhibition of ovulation 3. IUD (intrauterine device) or intrauterine hormone releasing system 8. Male patients must be sterilized or use a form of barrier contraception, such as condoms with spermicide, during the study and for 3 months after the last dose of study drug. 9. Life expectancy of ≥ 3 months. 10. Ability to provide written informed consent. 11. An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.	1. Patients with untreated or symptomatic brain metastases and/or leptomeningeal disease (exception: treated and stable brain metastases without symptoms for ≥ 2 weeks after completion of treatment, image documentation is required, and the patient must not be taking steroids). 2. Patients with a previous history of another malignancy (other than cured basal cell or squamous cell carcinoma of the skin or cured in-situ carcinoma) within 3 years of study entry. 3. Patients with uncontrolled pleural effusions, pericardial effusion, or ascites that do not resolve. 4. Patients with gastrointestinal tract disease causing the inability to take oral medication (e.g., swallowing difficulties, malabsorption syndromes, extensive small bowel resection \[\> 100cm\], gastric bypass surgery). 5. Pregnant or breast-feeding patients or any patient with child-bearing potential not using adequate contraception. 6. Known human immunodeficiency virus, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (excluding cured HBV and/or cured HCV infection). 7. Presence of any serious concomitant systemic disorders incompatible with the study in the opinion of the Investigator (e.g., uncontrolled congestive heart failure, active infection). 8. Radiation therapy to \> 30% of bone marrow within 3 months before study entry. 9. Patients with clinically significant autoimmune disease, either currently present of present within 2 years, including a current requirement for systemic immunosuppressive therapy equivalent to \> 10 mg/prednisone daily (local immunosuppressive therapy such as inhaled or topical corticosteroids is allowed). 11. Patients with abnormal or clinically significant electrocardiogram (ECG) abnormality, including but not limited to a confirmed corrected QT interval using Fridericia's formula (QTcF) \> 470 msec. 12. Patient has received systemic anticancer therapy within 3 weeks or 5 half-lives, whichever is shorter. 13. Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. 14. Any of the following conditions (on-study testing is not required): 15. Administration of strong or moderate cytochrome (CYP) 3A4 inhibitors and inducers within 14 days or 5 half-lives (whichever is shorter) prior to the administration of study drug.

Inclusion Criteria

Exclusion Criteria

1. Adults ≥ 18 years of age. Patient has TNBC; OR platinum-resistant HGSOC, primary peritoneal cancer, and/or fallopian-tube cancer; OR serous endometrial cancer, as described below.
2. TNBC:
1. Histologically or cytologically confirmed metastatic or locally recurrent unresectable TNBC per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria.
2. TNBC must have TP53 mutation/loss and be relapsed/refractory to at least 1 line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or be intolerant of existing therapy(ies). Prior exposure to an immune checkpoint inhibitor is allowed.
3. Platinum-resistant HGSOC, primary peritoneal cancer, and/or fallopian-tube cancer:
1. Histologically or cytologically confirmed diagnosis of metastatic or unresectable HGSOC, with TP53 mutation/loss, with platinum resistance defined as progression during or within 6 months of a platinum containing regimen, with no other standard treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed.
2. Patients whose tumors have progressed after at least 1 line of therapy for advanced/metastatic settings.
3. Systemic therapy with a PARP inhibitor will be counted as 1 line of therapy. Induction followed by maintenance will be counted as 1 line of therapy.
4. Serous endometrial cancer:
5. Measurable disease per RECIST v1.1
6. Adequate bone marrow reserve, cardiac, liver, and renal function:
7. Female patients of child-bearing potential must have a negative serum pregnancy test and use at least 1 form of acceptable birth control method listed below as approved by the Investigator before initiating study treatment and for 3 months after the last dose of study drug.
1. Sterilization
2. Any hormonal contraceptives (non-CYP 3A4 inhibitors) associated with inhibition of ovulation
3. IUD (intrauterine device) or intrauterine hormone releasing system
8. Male patients must be sterilized or use a form of barrier contraception, such as condoms with spermicide, during the study and for 3 months after the last dose of study drug.
9. Life expectancy of ≥ 3 months.
10. Ability to provide written informed consent.
11. An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.

1. Patients with untreated or symptomatic brain metastases and/or leptomeningeal disease (exception: treated and stable brain metastases without symptoms for ≥ 2 weeks after completion of treatment, image documentation is required, and the patient must not be taking steroids).
2. Patients with a previous history of another malignancy (other than cured basal cell or squamous cell carcinoma of the skin or cured in-situ carcinoma) within 3 years of study entry.
3. Patients with uncontrolled pleural effusions, pericardial effusion, or ascites that do not resolve.
4. Patients with gastrointestinal tract disease causing the inability to take oral medication (e.g., swallowing difficulties, malabsorption syndromes, extensive small bowel resection \[\> 100cm\], gastric bypass surgery).
5. Pregnant or breast-feeding patients or any patient with child-bearing potential not using adequate contraception.
6. Known human immunodeficiency virus, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (excluding cured HBV and/or cured HCV infection).
7. Presence of any serious concomitant systemic disorders incompatible with the study in the opinion of the Investigator (e.g., uncontrolled congestive heart failure, active infection).
8. Radiation therapy to \> 30% of bone marrow within 3 months before study entry.
9. Patients with clinically significant autoimmune disease, either currently present of present within 2 years, including a current requirement for systemic immunosuppressive therapy equivalent to \> 10 mg/prednisone daily (local immunosuppressive therapy such as inhaled or topical corticosteroids is allowed).
11. Patients with abnormal or clinically significant electrocardiogram (ECG) abnormality, including but not limited to a confirmed corrected QT interval using Fridericia's formula (QTcF) \> 470 msec.
12. Patient has received systemic anticancer therapy within 3 weeks or 5 half-lives, whichever is shorter.
13. Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline.
14. Any of the following conditions (on-study testing is not required):
15. Administration of strong or moderate cytochrome (CYP) 3A4 inhibitors and inducers within 14 days or 5 half-lives (whichever is shorter) prior to the administration of study drug.

Contacts and Locations

Study Contact

Dr. Sotirios Stergiopoulos, MD, CEO

CONTACT

718-570-5029

clinicaltrials@a2apharma.net

Robbin Frnka, VP/Clinops

CONTACT

214-205-5746

rfrnka@a2apharma.net

Study Locations (Sites)

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Oklahoma Univeristy

Oklahoma City, Oklahoma, 73104

United States

Mary Crowley Cancer Research

Dallas, Texas, 75230

United States

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030

United States

Next Oncology -Virginia

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: A2A Pharmaceuticals Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-11-02

Study Completion Date2027-01-27

Study Record Updates

Study Start Date2023-11-02

Study Completion Date2027-01-27

Terms related to this study

Additional Relevant MeSH Terms

Triple Negative Breast Cancer
High Grade Serous Ovarian Cancer
Endometrial Cancer