Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Carcinoma

Calculi

Carcinoma, Adenoid Cystic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adenoid Cystic Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

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.

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.

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

CB-103

Abemaciclib

Glenn Hanna, MD

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.

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

A Phase 1/2 Study of CB-103 (Oral Pan-NOTCH Inhibitor) With Abemaciclib or Lenvatinib in Combination in Patients With NOTCH Activated Adenoid Cystic Carcinoma (CALCulus)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

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) 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.

Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Overall Survival (OS) is defined as the time from study registration to death due to any cause, or censored at date last known alive.

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).

Adenoid Cystic Carcinoma Research Foundation

Cellestia Biotech AG

Glenn J. Hanna

Principal Investigator

Disease Attributes

* Dose Escalation: Participants will receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)-422, oral capsule administered once daily
* Dose Expansion: Participants will receive REM-422 at the identified RP2D
* Treatment will continue until disease progression, therapy intolerance, or participant withdrawal
* Safety evaluation will continue until 30 days of last administration of REM-422

* REM-422 is a first in class, small molecule mRNA inhibitor that reduces expression of the MYB transcription factor
* REM-422 will be administered orally once daily

REM-422

Barb Geiger, BSN

Rosalie Jiang

Hyunseok Kang, MD

Paul L Swiecicki, MD

Alan L Ho, MD, PhD

Meredith McKean, MD

Renata Ferrarotto, MD

Christopher Bowden, MD

The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with advanced Adenoid Cystic Carcinoma (ACC)

This is a Phase 1, open-label, non-randomized, multicenter study investigating REM-422, a potent, selective, and oral small molecule mRNA degrader that reduces expression of the MYB transcription factor for patients with recurrent or metastatic ACC.

This study includes a Dose Escalation Phase and a Dose Expansion Phase. The purpose of the Dose Escalation Phase is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REM-422 in patients with recurrent or metastatic ACC. The purpose of Dose Expansion is to further evaluate the safety and anti-tumor activity of the RP2D carried forward from Dose Escalation.

Participation in this study will continue until disease progression, therapy intolerance, or participant withdrawal.

Study of REM-422 in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

A Phase 1, Multicenter, Open-label Study of REM-422, a MYB mRNA Degrader, in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and number of participants with Dose Limiting Toxicities will be assessed to determine Safety and Tolerability of REM-422

Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and the number of participants with Dose Limiting Toxicities will be assessed

ORR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422

PFS will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422

DoR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422

TTR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422

DCR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422

mOS will be evaluated after treatment with REM-422

Measure Maximal concentration (Cmax) of REM-422

Measure Minimal concentration (Cmin) of REM-422

Measure Time to peak drug concentration (Tmax) of REM-422

Measure Area Under the Curve (AUC) of REM-422

Remix Therapeutics

Disease Progression

Avelumab

Axitinib

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive axitinib PO BID on days 1-28 and avelumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Renata Ferrarotto

This phase II trial studies how well axitinib and avelumab work in treating patients with adenoid cystic carcinoma that has come back or spread to other places in the body. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving axitinib and avelumab together may help to control adenoid cystic carcinoma.

PRIMARY OBJECTIVES:

I. Assess the objective response rate (ORR) to axitinib and avelumab combination according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria patients with recurrent or metastatic adenoid cystic carcinoma (ACC) who have evidence of disease progression within 6 months prior to study enrollment.

SECONDARY OBJECTIVES:

I. Assess ORR to axitinib and avelumab combination according to immune-related (ir)RECIST criteria patients with recurrent or metastatic adenoid cystic carcinoma (ACC).

II. Evaluate median progression free survival (PFS), PFS rate at 6 months after start of treatment.

III. Evaluate median overall survival (OS), OS rate at 6 months after start of treatment.

IV. Evaluate duration of response (DoR). V. Evaluate safety and toxicity.

EXPLORATORY OBJECTIVES:

I. Assess molecular markers associated with response and resistance to the study combination using tissue and/or plasma obtained from study participants.

OUTLINE:

Patients receive axitinib orally (PO) twice daily (BID) on days 1-28 and avelumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days and then every 6 months thereafter.

Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

A Phase 2 Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma (ACC)

Will be evaluated per Response Evaluation Criteria in Solid Tumors 1.1 criteria. The trial will be conducted by Simon's 2-stage design and the response rate will be estimated after the second stage. The response rate will be estimated along with its 95% confidence interval.

Will be estimated using the method of Kaplan and Meier.

Toxicity is defined as adverse events in the first 4 weeks that are judged to be attributable to one agent or both in combination.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CB-103 With Either Lenvatinib or Abemaciclib in Patients With NOTCH ACC	NCT05774899	Adenoid Cystic ... Metastatic Aden... Recurrent Adeno...	CB-103 Abemaciclib Lenvatinib	18 Years -	Dana-Farber Cancer Institute
Study of REM-422 in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma	NCT06118086	Adenoid Cystic ... Metastatic Aden... Recurrent Adeno...	REM-422	18 Years -	Remix Therapeutics
Study of REM-422 in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma	NCT06118086	Adenoid Cystic ... Metastatic Aden... Recurrent Adeno...	REM-422	18 Years -	Remix Therapeutics
Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma	NCT03990571	Metastatic Aden... Progressive Dis... Recurrent Adeno...	Avelumab Axitinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for recurrent adenoid cystic carcinoma