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) * Abemaciclib (CDK4/6 inhibitor) * Lenvatinib (a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI))
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 CDK4/6 inhibitor, Abemaciclib, 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 + Abemaciclib or Cohort 2: VEGFR TKI Lenvatinib + CB-103. The U.S. Food and Drug Administration (FDA) has not approved CB-103 as a treatment for any disease. The FDA has not approved Abemaciclib 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
First-in-class pan-NOTCH inhibitor, capsule taken orally.
CDK4/6 inhibitor, tablet taken orally.
Per standard care, capsule taken orally.
Dana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGProgression-Free Survival (PFS) of Cohort 1
Progression-Free Survival (PFS) is defined as the time from study registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Median PFS will be estimated via the Kaplan-Meier method to estimate all time-to-event endpoints with corresponding 95% confidence intervals (CI) for the median or time-specific event time
Time frame: At 4 months
Progression-Free Survival (PFS) of Cohort 2
Progression-Free Survival (PFS) is defined as the time from study registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Time frame: At 4 months
Number of Participants with treatment related Adverse Events per CTCAE 5.0
Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: Up to 2 years
Overall Response Rate (ORR)
Per RECIST v1.1
Time frame: From enrollment to end of treatment up to 2 years
Overall Survival (OS)
Overall Survival (OS) is defined as the time from study registration to death due to any cause, or censored at date last known alive.
Time frame: Up to 2 years
Duration of Overall Response (DOR)
The duration of overall response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR), whichever is first recorded, until the first date that recurrent or progressive disease is objectively documented. Participants without events reported are censored at the last disease evaluation).
Time frame: Up to 2 years
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