Grant Award Details
- The objective of this award is to evaluate the safety and tolerability of orally administered TACH101, a small molecule targeting KDM4, and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of TACH101 in patients with solid tumors.
Grant Application Details
- TACH101: A Potent, First-In-Class KDM4 Inhibitor for Advanced Cancers
Therapeutic Candidate or Device
TACH101 is a first-in-class small molecule inhibitor of KDM4 histone demethylase, an epigenetic modifier important for cancer stem cell proliferation.
TACH101 is intended to target colorectal cancer (CRC) stem cells as well as the bulk tumor by inhibiting proliferation. In CRC animal models, TACH101 treatment reduced the number of cells with cancer stem cell features and reduced the number of tumor-initiating cells. TACH101 also significantly slowed tumor growth in CRC models and showed high sensitivity in CRC with Microsatellite Instability High (MSI-H) status.
Unmet Medical Need
Late stage CRC patients receive chemotherapy with survival typically not exceeding 2 yrs. TACH101 showed potent anti-tumor activity in CRC animal models, including MSI-H CRC which accounts for 15% of cases and do not respond to chemotherapy due to deficiency in DNA repair mechanisms.
Phase 1a/1b trial completed
Major Proposed Activities
- Complete Phase 1a dose escalation study to assess safety and recommended phase 2 dose (RP2D) of TACH101
- Complete Phase 1b dose expansion study to assess effect of TACH101 in specific cancer types (CRC and GI cancers)
- Complete analyses of blood samples from enrolled patients to assess genomic biomarkers that may inform of a responder population
California has a CRC incidence rate of ~32 per 100,000 people per year. With a population of ~39 million people, ~12,500 have CRC and about 22% will be diagnosed with late stage disease (SEER 2022). Thus, TACH101 has the potential to help ~2,750 advanced CRC patients in CA a year. In addition, the proposed project plan utilizes California-based resources (e.g., clinical site, PK vendor, Biomarker vendor, Manufacturing vendor), aligning with CIRM's mission to support CA-based infrastructure.