A study of MT-4561 in patients with various advanced solid tumors (NCT06943521).

TPS3178 Background: MT-4561 is a bromodomain-containing protein 4 (BRD4) protein degrader, which is a bi-functional molecule having both a binder moiety that binds to BRD4 and a degron moiety that binds to damage-specific deoxyribonucleic acid (DNA) binding protein 1 (DDB1) and cullin 4 (CUL4) associated factor 16 (DCAF16), which is responsible for the ubiquitination of BRD4. MT-4561 degrades BRD4, a bromodomain protein that stimulates oncogene transcription, using the ubiquitin-proteasome system. Tanabe Pharma has demonstrated that this novel BRD4 degrader, MT-4561, exerts continuous anti-tumor effects in various cancer xenograft models (Ooike, 2024). Methods: This trial is a FIH, Phase I/II study to evaluate safety, tolerability, PK, PD, and efficacy of MT-4561 in patients with advanced solid tumors. Part 1 is evaluating safety, tolerability, PK, MTD, and the doses to be investigated in Part 2 (dose optimization) using the BOIN design. Part 2 evaluates the safety and efficacy of MT-4561 in patients with pre-specified tumor types based on data from Part 1, and to determine the RP2D. Part 2 can begin enrollment after the MTD and/or the doses to be investigated in Part 2 have been determined based on data from Part 1. Part 3 of the study is the open-label drug-drug interaction (DDI) cohort to evaluate the effect of MT-4561 on the PK established in Part 1. A retrospective analysis will also be conducted to assess the correlation between efficacy and expression of BRD4/its downstream gene products in patient samples to explore predictive biomarkers. MT-4561 is administered as an intravenous (IV) infusion over 30 minutes once every week in 28-day cycles, until disease progression or discontinuation criteria are met. Parts 1 and 3 of the study will enroll patients 18 years and older with who have failed at least 1 therapy , who have ≥ 1 measurable lesion by RECIST v1.1 and with confirmed histologic or cytologic diagnosis of one of the following tumors: HNSCC, NSCLC, esophageal cancer, gastric cancer, biliary tract cancer, PDAC, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, prostate cancer, urothelial carcinoma, NET or NEC, soft tissue sarcoma, and NUT carcinoma. Part 2 will enroll only pre-specified tumors for dose optimization to determine the RP2D. Key exclusion criteria include patients with unresolved ≥ Grade 2 toxicities from previous treatment and those with QTc prolongation > 470 msec at screening. Also, patients who received drugs with a known risk of QT interval prolongation or torsade de pointes, before the start of IMP administration. Enrollment in Part 1 of the study began May 2025 and continues to enroll patients in the US and Japan with 10 patients enrolled through Dose Level 2 as of Jan 2026. The safety data along with DLT continues to be reviewed in Part 1. Ooike S, et al. PB069, Poster Session, 36th EORTC-NCI-AACR Symposium, 2024. Clinical trial information: NCT06943521 .