CB-103 With Either Lenvatinib or Abemaciclib in Patients With NOTCH ACC

NCT05774899 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 23-011
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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))

Conditions

Adenoid Cystic Carcinoma; Metastatic Adenoid Cystic Carcinoma; Recurrent Adenoid Cystic Carcinoma

Keywords

Adenoid Cystic Carcinoma; Metastatic Adenoid Cystic Carcinoma; Recurrent Adenoid Cystic Carcinoma; ACC

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  At 4 months

Secondary Outcomes (4)

• Number of Participants with treatment related Adverse Events per CTCAE 5.0

  Up to 2 years

• Overall Response Rate (ORR)

  From enrollment to end of treatment up to 2 years

• Overall Survival (OS)

  Up to 2 years

• Duration of Overall Response (DOR)

  Up to 2 years

Study Arms (4)

Experimental: Cohort 1A - CB-103 + Abemaciclib

EXPERIMENTAL

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.

Drug: CB-103; Drug: Abemaciclib

Experimental: Cohort 1B - CB-103 + Abemaciclib

EXPERIMENTAL

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.

Drug: CB-103; Drug: Abemaciclib

Experimental: Cohort 2A- Lenvatinib + CB-103

EXPERIMENTAL

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.

Drug: CB-103; Drug: Lenvatinib

Experimental: Cohort 2B- Lenvatinib + CB-103

EXPERIMENTAL

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.

Drug: CB-103; Drug: Lenvatinib

Interventions

CB-103 DRUG

First-in-class pan-NOTCH inhibitor, capsule taken orally.

Experimental: Cohort 1A - CB-103 + Abemaciclib; Experimental: Cohort 1B - CB-103 + Abemaciclib; Experimental: Cohort 2A- Lenvatinib + CB-103; Experimental: Cohort 2B- Lenvatinib + CB-103

Abemaciclib DRUG

CDK4/6 inhibitor, tablet taken orally.

Experimental: Cohort 1A - CB-103 + Abemaciclib; Experimental: Cohort 1B - CB-103 + Abemaciclib

Lenvatinib DRUG

Per standard care, capsule taken orally.

Also known as: Lenvima

Experimental: Cohort 2A- Lenvatinib + CB-103; Experimental: Cohort 2B- Lenvatinib + CB-103

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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)
• The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
• Pregnant or lactating women. Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued.
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and start of therapy. Patients on anticoagulants that require INR monitoring (such as warfarin). The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, or is currently enrolled in any other type of medical research judged by the sponsor not to be scientifically or medically compatible with this study.
• Corrected QTcF \>450 msec for males and \>470 msec for females in screening

Sponsors & Collaborators

• Glenn J. Hanna: lead
• Adenoid Cystic Carcinoma Research Foundation: collaborator
• Cellestia Biotech AG: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

abemaciclib; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Glenn Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn Hanna, MD

CONTACT

617-632-3090; Gjhanna@partners.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: March 20, 2023
• Study Start: June 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)