AO-252 / A2A Pharma, OncoCube Therap - LARVOL DELTA

TACC3 is a driver of metastasis in centrosome-amplified breast cancer (AACR-NCI-EORTC 2025) - "Importantly, pharmacologic inhibition with AO252, clinical grade TACC3 inhibitor or CRISPR-Cas9–mediated knockout of TACC3 disrupts these interactions and significantly impairs invasive behavior...Together, our findings establish TACC3 as a druggable driver of metastasis in centrosome-amplified breast cancer and offer new mechanistic insights. This work highlights a novel therapeutic strategy for halting metastasis in a highly aggressive breast cancer subtype."

Breast Cancer • Oncology • Solid Tumor • Thoracic Cancer • CTCs • TACC3

A First-In-Human, Phase 1 Study Evaluating Oral TACC3 PPI Inhibitor, AO-252, in Advanced Solid Tumors With or Without Brain Metastases (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: A2A Pharmaceuticals Inc. | N=144 ➔ 86 | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Oct 2025 ➔ Jan 2027

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Brain Cancer • Oncology • Solid Tumor

Novel TACC3 protein-protein interaction inhibitor, AO-252, shows potent activity in prostate, gastric cancers, and triple negative breast cancer with brain metastasis (AACR 2025) - P1 | "AO-252 is currently in first-in-human (FIH), Phase I clinical trial in TNBC, ovarian and endometrial cancers (NCT06136884). We are in the process of expanding our trial to include prostate, gastric cancer and TNBC with brain metastases."

Breast Cancer • Endometrial Cancer • Gastric Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARNT • BRCA1 • EGFR • HDAC2 • KIFC1 • TACC3

A2A Pharmaceuticals, Inc. Announces Phase 1 Clinical Trial Advancements in TACC3 Inhibition Program Targeting Multiple Cancers (PRNewswire) - "A2A Pharmaceuticals...announced significant progress in its clinical studies exploring TACC3 (Transforming Acidic Coiled-Coil 3) inhibition in patients with ovarian cancer, triple-negative breast cancer (TNBC), and endometrial cancer, as well as other malignancies. A2A Pharmaceuticals has progressed into cohort 4, an important inflection point in its Phase 1 clinical trial to assess the safety and efficacy of its lead TACC3 inhibitor, A0-252. Early results have shown strong safety and efficacy profiles with the potential for a wide therapeutic index in these patient populations."

Trial status • Endometrial Cancer • Ovarian Cancer • Triple Negative Breast Cancer

A2A Pharmaceuticals, Inc. Announces Phase 1 Clinical Trial Advancements in TACC3 Inhibition Program Targeting Multiple Cancers (BioSpace) - "'This trial represents a promising step forward in delivering therapies that could impact the standard of care for patients,' said Alex Spira...'A2A Pharmaceuticals is committed to supporting the cancer community by advancing novel therapies that target the underlying biology of tumors.'"

Media quote

A first-in-human, phase 1 study evaluating oral TACC3 inhibitor, AO-252, in advanced solid tumors. (ASCO 2024) - P1 | "Potential biomarkers relating to treatment outcome will be evaluated as exploratory endpoints. Enrollment in Cohort 1 is completed and enrollment to Cohort 2 will begin in February 2024."

Metastases • P1 data • Endometrial Cancer • Oncology • Ovarian Serous Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer • KIFC1 • TACC3 • TP53