Undisclosed PKMYT1 inhibitor / Roche - LARVOL DELTA

Discovery of selective and orally bioavailable PKMYT1 inhibitor: characterization of anti-tumor activities as single and dual agents (AACR 2025) - "Preclinical validation of this hypothesis demonstrated that combining PKMYT1 inhibitors with ATR inhibitors, such as prexasertib and RP-3500, resulted in enhanced antitumor activity in CCNE1-amplified cancer models. Additionally, we observed synergistic effects when combining PKMYT1 inhibitors with standard-of-care chemotherapies that induce DNA damage, such as gemcitabine and hydroxyurea...In conclusion, our study underscores the therapeutic potential of selective PKMYT1 inhibitors in CCNE1-amplified cancers and provides a strong rationale for their combination with ATR inhibitors and DNA-damaging chemotherapies. These findings support the continued development and clinical evaluation of PKMYT1 inhibitors as a novel approach to cancer treatment."

Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • CCNE1 • CDK1 • PKMYT1