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))
Participants must have histologically confirmed adenoid cystic carcinoma (ACC) with evidence of recurrent, metastatic or advanced, incurable disease arising from any primary site
Activating mutation in the NOTCH signaling pathway
In Cohort 1 only, prior multitargeted VEGFR TKI or systemic therapy is permitted.
In Cohort 2 only, no prior multitargeted VEGFR TKI therapy is permitted, but prior systemic chemotherapy as part of definitive or curative intent management is permitted.
Participant has untreated or clinically symptomatic CNS metastases and/or carcinomatous meningitis
The patient has had major surgery within 14 days prior to study registration.
The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
Impairment of GI function or presence of GI disease that may significantly alter the absorption of the study agents (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
Parallel
CB-103
DrugFirst-in-class pan-NOTCH inhibitor, capsule taken orally.
Abemaciclib
DrugCDK4/6 inhibitor, tablet taken orally.
Lenvatinib
DrugPer standard care, capsule taken orally.
Progression-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
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.
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
Overall Response Rate (ORR)
Per RECIST v1.1
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.
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).
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Michael J. Dennis, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Adenoid Cystic Carcinoma Research Foundation
Collaborator
Cellestia Biotech AG
Collaborator
