A First-In-Human, Phase 1 Study Evaluating Oral TACC3 PPI Inhibitor, AO-252, in Advanced Solid Tumors With or Without Brain Metastases

NCT06136884 | Recruiting Phase 1 FDA Drug

• 1 other identifier: A2A-O-004
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Solid Tumor Malignancies; Brain Metastases From Solid Tumors

Keywords

brain metastases; solid tumors; AO-252

Outcome Measures

Primary Outcomes (6)

• Safety Assessments [Dose escalation]

  Incidence of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects

  12 months

• Safety Assessments [Dose escalation]

  Identify the maximum tolerated dose and the doses for expansion

  12 months

• Safety Assessments [Dose escalation and Dose expansion]

  Number of participants with Serious Adverse Events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  30 months

• Safety Assessments [Dose escalation and Dose expansion]

  Number of participants with Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0

  30 months

• Safety Assessments [Dose escalation and Dose expansion]

  Number of participants with Treatment-Emergent AEs (TEAEs) graded per NCI-CTCAE version 5.0

  30 months

• Safety Assessments [Dose escalation and Dose expansion]

  Number of participants with Dose Interruptions and Permanent Treatment Discontinuations

  30 months

Secondary Outcomes (7)

• Antitumor Activity of AO-252 [Dose escalation and Dose expansion]

  30 months

• Antitumor Activity of AO-252 [Dose escalation and Dose expansion]

  30 months

• Antitumor Activity of AO-252 [Dose escalation and Dose expansion]

  30 months

• Antitumor Activity of AO-252 [Dose escalation and Dose expansion]

  30 months

• Pharmacokinetic Profile of AO-252 [Dose escalation and Dose expansion]

  30 months

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

Participants will be assigned to dose levels.

Drug: AO-252

Part 2: Dose Expansion

EXPERIMENTAL

After doses are decided in Part 1, participants entering part 2 will be assigned to a dose level.

Drug: AO-252

Interventions

AO-252 DRUG

AO-252 will be administered oral tablets or capsules daily

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years of age.
• Patient has histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumors with TP53 mutation/loss and with/without brain metastasis. Patients must have relapsed/be refractory to at least 1 line of systemic therapy in the metastatic setting (excluding melanoma).
• Prostate cancer:
• mCRPC with histologic confirmation of adenocarcinoma. mCRPC with neuroendocrine features or mixed histology are excluded
• Patients will be enrolled irrespective of the TP53 status
• Participant must have prostate specific antigen (PSA) of ≥ 2 ng/mL
• Is surgically or medically castrated, with testosterone levels of less than 50 ng/dL
• Patients who progressed on at least 1 prior novel androgen receptor AR-targeted therapy (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), and or at least 1 prior systemic chemotherapy (e.g., docetaxel)
• Solid tumors with brain metastasis:
• Histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumors excluding melanoma with TP53 mutation/loss and tumor must have relapsed/be refractory to at least 1 line of systemic therapy. Untreated brain metastases not requiring immediate local CNS therapy
• Previously treated brain metastases with progression of previous lesions or new lesions, but not requiring immediate local CNS therapy
• At least one measurable untreated brain lesion ≥0.5 cm and \<3.0 cm in the longest axis
• Prior SRS radiosurgery (must be completed within 7 days of study treatment initiation) is allowed as long as the previous treatment volume does not overlap with the current targets.
• Measurable disease per RECIST v1.1 criteria. For mCRPC patients, tumor response will be evaluated using RECIST version 1.1 (soft tissue) and PCWG-3 criteria (bone) and efficacy endpoints will also include radiographic progression-free survival (rPFS), PSA50 response and PSA progression
• Adequate bone marrow reserve, cardiac, liver, and renal function:

You may not qualify if:

• Patients with symptomatic brain metastases requiring treatment and/or leptomeningeal disease
• 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.
• Patients with uncontrolled pleural effusions, pericardial effusion, or ascites that do not resolve.
• 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).
• Pregnant or breast-feeding patients or any patient with child-bearing potential not using adequate contraception.
• Known human immunodeficiency virus, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (excluding cured HBV and/or cured HCV infection).
• 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).
• Radiation therapy to \> 30% of bone marrow within 3 months before study entry.
• 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).
• \. 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.
• \. Patient has received systemic anticancer therapy within 3 weeks or 5 half-lives, whichever is shorter.
• \. Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline.
• \. Any of the following conditions (on-study testing is not required):
• \. 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.

Sponsors & Collaborators

• A2A Pharmaceuticals Inc.: lead

Study Sites (5)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Oklahoma Univeristy

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

RECRUITING

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Next Oncology -Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Robbin Frnka, Chief ClinOps Officer

CONTACT

2142055746; rfrnka@coiledtx.com; rfrnka@a2apharma.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 18, 2023
• Study Start: November 2, 2023
• Primary Completion (Estimated): January 28, 2027
• Study Completion (Estimated): January 27, 2028
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)