This is a phase 2, open-label, non-randomized, parallel cohort, multicenter study investigating the novel pan-NOTCH inhibitor, CB-103, in combination with the BCL2 inhibitor, Venetoclax, and CB-103 in combination with the multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Lenvatinib for patients with advanced, incurable, or metastatic adenoid cystic carcinoma (ACC) with a Notch pathway activating mutation.~Participants will be placed into one of two treatment groups: Cohort 1: CB-103 + Venetoclax or Cohort 2: VEGFR TKI Lenvatinib + CB-103. Cohort 1 will enroll participants who have not received treatment for ACC while Cohort 2 will enroll participants immediately after receiving Lenvatinimb and after showing prior disease progression.~The U.S. Food and Drug Administration (FDA) has not approved CB-103 as a treatment for any disease.~The FDA has not approved Venetoclax or Lenvatinib for advanced adenoid cystic carcinoma (ACC)), but it has been approved for other uses or cancer types.~Study procedures include screening for eligibility, treatment visits, radiologic scans of tumors, and blood tests.~Participation in this study is expected to last about 2 years or until disease progression, therapy intolerance, or participant withdrawal.~It is expected that about 32 people will take part in this research study.~Cellestia Biotech AG is supporting this research study by providing funding.
The goal of this study is to treat patients with NOTCH active advanced adenoid cystic carcinoma (ACC) tumors with a combination or two different oral medications to slow tumor growth and improve survival outcomes.~The names of the study drugs involved in this study are:~CB-103 (an oral NOTCH pathway inhibitor)~Venetoclax (a BCL-2 inhibitor)~Lenvatinib (a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI))