CB-103 With Either Lenvatinib or Abemaciclib in Patients With NOTCH ACC
- Conditions
- Adenoid Cystic CarcinomaMetastatic Adenoid Cystic CarcinomaRecurrent Adenoid Cystic Carcinoma
- Interventions
- Registration Number
- NCT05774899
- Lead Sponsor
- Glenn J. Hanna
- Brief Summary
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))
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental: Cohort 1A - CB-103 + Abemaciclib Abemaciclib A modified 3+3 dose escalation design will be used. 3-9 participants will receive: * Standard of care Abemaciclib. * Cycle 1 - End of Treatment --Days 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week. * A safety review will be performed by primary investigation after completion of the ramp-up phase. Experimental: Cohort 1B - CB-103 + Abemaciclib Abemaciclib Participants will receive: * Cycle 1 - End of Treatment --Days 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week and predetermined dose of Abemaciclib 1x daily. * Therapy will continue until disease progression, therapy intolerance, or participant withdrawal. * End of Treatment (EOT) visit within 30 days of last administration of study treatments. Experimental: Cohort 2A- Lenvatinib + CB-103 Lenvatinib A modified 3+3 dose escalation design will be used. 3-9 participants will receive: * Standard of care VEGFR TKI. * Cycle 1 - End of Treatment --Days 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week. * A safety review will be performed by primary investigation after completion of the ramp-up phase. Experimental: Cohort 2B- Lenvatinib + CB-103 Lenvatinib Participants will receive: * Continue standard of care VEGFR TKI at prior dose and schedule. * Cycle 1 - End of Treatment --Day 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week. * Therapy will continue until disease progression, therapy intolerance, or participant withdrawal. * End of Treatment (EOT) visit within 30 days of last administration of study treatments. Experimental: Cohort 1A - CB-103 + Abemaciclib CB-103 A modified 3+3 dose escalation design will be used. 3-9 participants will receive: * Standard of care Abemaciclib. * Cycle 1 - End of Treatment --Days 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week. * A safety review will be performed by primary investigation after completion of the ramp-up phase. Experimental: Cohort 2A- Lenvatinib + CB-103 CB-103 A modified 3+3 dose escalation design will be used. 3-9 participants will receive: * Standard of care VEGFR TKI. * Cycle 1 - End of Treatment --Days 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week. * A safety review will be performed by primary investigation after completion of the ramp-up phase. Experimental: Cohort 1B - CB-103 + Abemaciclib CB-103 Participants will receive: * Cycle 1 - End of Treatment --Days 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week and predetermined dose of Abemaciclib 1x daily. * Therapy will continue until disease progression, therapy intolerance, or participant withdrawal. * End of Treatment (EOT) visit within 30 days of last administration of study treatments. Experimental: Cohort 2B- Lenvatinib + CB-103 CB-103 Participants will receive: * Continue standard of care VEGFR TKI at prior dose and schedule. * Cycle 1 - End of Treatment --Day 1- 28 of 28-day cycle: Predetermined dose of CB-103 2x daily on five consecutive days followed by two days of treatment break in each treatment week. * Therapy will continue until disease progression, therapy intolerance, or participant withdrawal. * End of Treatment (EOT) visit within 30 days of last administration of study treatments.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) of Cohort 1 At 4 months 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 At 4 months 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.
- Secondary Outcome Measures
Name Time Method Number of Participants with treatment related Adverse Events per CTCAE 5.0 Up to 2 years Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Overall Response Rate (ORR) From enrollment to end of treatment up to 2 years Per RECIST v1.1
Overall Survival (OS) Up to 2 years 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) Up to 2 years 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).
Trial Locations
- Locations (1)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States