Trial Title:
A First-In-Human, Phase 1 Study Evaluating Oral TACC3 PPI Inhibitor, AO-252, in Advanced Solid Tumors
NCT ID:
NCT06136884
Condition:
Triple Negative Breast Cancer
High Grade Serous Ovarian Cancer
Endometrial Cancer
Conditions: Official terms:
Endometrial Neoplasms
Triple Negative Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AO-252
Description:
AO-252 will be administered oral tablets daily
Arm group label:
Part 1: Dose Escalation
Arm group label:
Part 2: Dose Expansion
Summary:
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.
Detailed description:
The purpose of this study is to characterize the safety, tolerability including
determination of maximum tolerated dose (MTD), and identify the recommended Phase 2 dose
(RP2D). The study will also look at pharmacokinetics (PK), pharmacodynamics (PD) and
preliminary anti-tumor activity of AO-252 as a monotherapy in participants with advanced
or metastatic triple negative breast cancer (TNBC), high- grade serous ovarian carcinoma
(HGSOC), and endometrial cancer
Criteria for eligibility:
Criteria:
Inclusion 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:
a. Histologically or cytologically confirmed diagnosis of metastatic or recurrent
unresectable serous endometrial cancer with TP53 mutation/loss and tumor must have
relapsed/be refractory to at least 1 line of systemic therapy (including immune
checkpoint inhibitors) but no more than 4 lines of systemic therapy in the
metastatic/recurrent setting or be intolerant of existing therapy(ies) known to
provide clinical benefit for their condition.
5. Measurable disease per RECIST v1.1
6. Adequate bone marrow reserve, cardiac, liver, and renal function:
1. Absolute neutrophil count (ANC) ≥ 1,500/mm3
2. Platelet count ≥ 100,000/mm3
3. Hemoglobin ≥ 9 g/dL
4. Bilirubin ≤ 1.5 × upper limit of normal (ULN) or direct bilirubin ≤ ULN for
patients with total bilirubin levels >1.5 × ULN
5. Alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT)
≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present)
6. INR ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy and PT or
aPTT is within therapeutic range of intended use of anticoagulants
7. Serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 50 mL/min (by Cockroft
Gault formula).
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.
Exclusion Criteria:
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 before study entry.
9. Patients who require chronic systemic steroid therapy (> 10 mg prednisone daily or
equivalent) or those that are on any other form of immunosuppressive medication.
10. Patients with active autoimmune disease or with a documented history of autoimmune
disease.
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):
1. Known HIV-infected patients unless on effective anti-retroviral therapy with an
undetectable viral load within 6 months and no opportunistic infection within
the past 12 months, or
2. Known or suspected hepatitis B if active infection (patients with chronic
hepatitis B infection must have an undetectable HBV viral load on suppressive
therapy, if indicated; positive surface antibody alone is not an exclusion), or
3. Known or suspected hepatitis C infection that has not been treated and cured
unless currently on treatment with an undetectable viral load.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Oklahoma Univeristy
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Caldwell
Phone:
405-271-8001
Phone ext:
48171
Email:
Christina-Caldwell@ouhsc.edu
Facility:
Name:
Mary Crowley Cancer Research
Address:
City:
Dallas
Zip:
75230
Country:
United States
Status:
Recruiting
Contact:
Last name:
Angela Hotchkiss
Email:
ahotchkiss@marycrowley.org
Investigator:
Last name:
Mina Barve, MD
Email:
Principal Investigator
Facility:
Name:
The University of Texas M.D. Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Guoxin Feng
Email:
gfeng@mdanderson.org
Contact backup:
Last name:
Amber Kennon
Email:
amkennon@mdanderson.org
Facility:
Name:
Next Oncology -Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anthony Young
Email:
ayoung@nextoncology.com
Investigator:
Last name:
Alexander Spira, MD
Email:
Principal Investigator
Start date:
November 2, 2023
Completion date:
January 27, 2027
Lead sponsor:
Agency:
A2A Pharmaceuticals Inc.
Agency class:
Industry
Source:
A2A Pharmaceuticals Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06136884
