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

A Phase 1/2, Multicenter, Open-label Study of REM-422, a MYB mRNA Degrader, in Patients With Recurrent, Metastatic, or Unresectable Adenoid Cystic Carcinoma

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)

Study Overview

• Status: Recruiting
• Conditions: Adenoid Cystic Carcinoma; Metastatic Adenoid Cystic Carcinoma; Recurrent Adenoid Cystic Carcinoma
• Intervention / Treatment: Drug: REM-422

Detailed Description

This is a Phase 1/2, 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, metastatic, or unresectable ACC.

This study includes a Dose Escalation Phase and a Confirmatory Cohort 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 the Confirmatory Cohort is to further evaluate the safety and anti-tumor activity of the RP2D carried forward from Dose Escalation in patients with recurrent, metastatic, or unresectable ACC.

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

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rosalie Jiang; Phone Number: 781-584-9390; Email: rjiang@remixtx.com
• Study Contact Backup: Name: Remix Therapeutics; Phone Number: 781-827-0902; Email: ClinicalTrials@remixtx.com

Study Locations

• France
  • Nice, France, 06189
    • Not yet recruiting
    • Centre Antoine Lacassagne
    • Principal Investigator: Esma SAADA-BOUZID, MD
  • Villejuif, France, 94805
    • Not yet recruiting
    • Institut de Cancerologie Gustave-Roussy
    • Principal Investigator: Caroline Even, MD
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco Helen Diller Comprehensive Cancer Center
      • Principal Investigator: Hyunseok Kang, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Research Institute
      • Principal Investigator: Glenn Hanna, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
      • Principal Investigator: Paul L Swiecicki, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Alan L Ho, MD, PhD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Principal Investigator: Meredith McKean, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Renata Ferrarotto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be able to provide informed consent.
2. Be 18 years or older at the time of informed consent.

3. Disease criteria:

   1. Histologically confirmed ACC, any site of origin.

   2. Dose Escalation phase ONLY:

      • Have locally advanced or metastatic ACC
      • Evidence of radiographic progression and/or signs and symptoms associated with their disease (eg, pain, dyspnea, reduced performance status). Participants who have stable disease while being treated with another agent that is not tolerated are eligible after the appropriate washout period.

   3. Confirmatory Cohort phase ONLY:

      • Have metastatic, recurrent, or unresectable ACC
      • Measurable disease at the time of enrollment. At least 1 measurable lesion according to RECIST v1.1 criteria. Participants must have radiographic evidence of disease progression by RECIST v1.1 criteria ≤ 6 months prior to study enrollment. Radiographic eligibility as determined by Central IUO assay.
      • MYB poison exon biomarker positive tumor(s) confirmed by central IUO assay.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Tumor Tissue Requirements

   1. Dose Escalation Phase ONLY: be able to provide during Screening a tissue specimen of either a fresh biopsy of a non-target lesion or an archival tumor sample obtained within the last 6 years. A formalin-fixed paraffin-embedded (FFPE) block can be submitted or a minimum of 15 freshly sectioned unstained slides. Agree to an on-treatment biopsy to be obtained ~4-8 weeks after initiation of REM-422 unless medically contraindicated.
   2. Confirmatory Cohort phase ONLY: be able to provide, during Pre-Screening, a tissue specimen of either a fresh biopsy of non-targetable lesion or an archival tumor sample obtained within the last 6 years that is interpretable for the biomarker positivity. An FFPE block can be submitted or a minimum of 15 fresh sectioned unstained slides.
6. At least 3 weeks since prior systemic non-investigational therapy at the time of start of REM- 422.
7. Toxicities from prior therapy must be stable or recovered to ≤ Grade 1. Note: Stable chronic and clinically non-significant conditions (≤ Grade 2) that are not expected to resolve are exceptions (eg, neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies, etc.), and patients with these conditions may enroll.
8. Participants must be able to swallow and retain oral medications.
9. Oxygen saturation > 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with ≤ Grade 1 dyspnea.
10. Participants of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
11. Participants Of Child Bearing Potential must agree to use acceptable, effective methods of contraception as outlined in Appendix 1 and not donate ova from Screening until 6 months after discontinuation of REM- 422. Women who have undergone surgical or ablative sterilization or who have been postmenopausal for ≥ 2 years are not considered to be of childbearing potential.
12. Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-422.
13. Adequate bone marrow, organ function and laboratory parameters

Exclusion Criteria:

1. Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
2. Clinically significant active infection. Simple urinary tract infection, uncomplicated bacterial pharyngitis responding to active treatment are permitted. Participants receiving intravenous antibiotics ≤ 7 days prior to enrollment are excluded (prophylactic antibiotics, antivirals or antifungals are permitted).
3. Evidence of active HIV infection.
4. Evidence of currently active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
5. Primary immunodeficiency.
6. Current or expected need for daily systemic corticosteroid therapy ≥ 10 mg of prednisone equivalent. Topical or inhaled corticosteroids with minimal systemic absorption may enroll and continue minimal corticosteroids if the participant is on a stable dose.
7. Live vaccine ≤ 6 weeks prior to the start of REM-422.
8. Use of strong CYP3A inhibitors or CYP3A inducers
9. Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (e.g., omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study
10. Pregnancy or participants planning to become pregnant during the duration of the study, or lactation.
11. Participants with malabsorption syndrome, a disease significantly affecting gastrointestinal function, or resection of the stomach or bowel.
12. Current use of prohibited medication ≤ 1 week before starting REM-422.
13. Clinically significant cardiovascular disease:
14. Participants who have undergone major surgery (opening a mesenchymal barrier such as the pleural cavity, peritoneum, meninges, or surgical procedures requiring general anesthesia) < 4 weeks prior to enrollment.
15. History of organ transplant that requires use of immunosuppressive agents.
16. History or current autoimmune disease (eg, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
17. Radiation therapy ≤ 7 days prior to the start of REM-422.
18. Concurrent or previous other malignancy (other than adenoid cystic carcinoma, hematologic malignancies, or primary central nervous system [CNS] malignancies) ≤ 2 years of enrollment, except curatively treated malignancies including basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix.
19. Participants receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment.
20. Unwillingness or inability to follow protocol requirements.
21. Any condition that, in the opinion of the Investigator, would interfere with evaluation of REM-422 or interpretation of the participant's safety or study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: REM-422; 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; Ph 2 Confirmatory Cohort: 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

Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of Treatment Emergent Adverse Events (TEAEs)	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	18 months
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)	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	Assessed at the end of Cycle 1 for each participant
Overall Response Rate (ORR) in Phase 2 Confirmatory Cohort	ORR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	DoR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422	18 months
Time to Response (mTTR)	TTR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422	18 months
Median Overall Survival (mOS)	mOS will be evaluated after treatment with REM-422	18 months
Determine pharmacokinetic profile (Cmax) of REM-422	Measure Maximal concentration (Cmax) of REM-422	18 months
Determine pharmacokinetic profile (Cmin) of REM-422	Measure Minimal concentration (Cmin) of REM-422	18 months
Determine pharmacokinetic profile (Tmax) of REM-422	Measure Time to peak drug concentration (Tmax) of REM-422	18 months
Determine pharmacokinetic profile (AUC) of REM-422	Measure Area Under the Curve (AUC) of REM-422	18 months
Disease Control Rate (DCR)	DCR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422	6 months
Median Progression Free Survival (mPFS)	PFS will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422	6 months, 12 months

Collaborators and Investigators

• Sponsor: Remix Therapeutics
• Investigators: Study Chair: Mythili Koneru, MD, PhD, Remix Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Adenoid Cystic
• Other Study ID Numbers: REM-422-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No