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

Adenoid Cystic Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06118086
• Other study ID #: REM-422-101
• Status: Recruiting
• Phase: Phase 1
• Start date: December 20, 2023
• Est. completion date: June 1, 2026

Study information

• Verified date: January 2024
• Source: Remix Therapeutics
• Contact: Barb Geiger, BSN
• Phone: 913-206-2798
• Email: bgeiger[@]remixtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Be able to provide informed consent.

2. Be 18 or older at the time of informed consent.

3. Disease criteria:

• Histologically confirmed ACC, any site of origin.
• Have locally advanced or metastatic ACC.
• Dose Escalation phase ONLY: 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.
• Dose Expansion phase ONLY: 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.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. 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 months or longer if there has been no systemic interval therapy since the last biopsy. A formalin-fixed paraffin-embedded block can be submitted or a minimum of 15 freshly 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.

Related Conditions & MeSH terms

• Adenoid Cystic Carcinoma
• Carcinoma
• Carcinoma, Adenoid Cystic
• Metastatic Adenoid Cystic Carcinoma
• Recurrence
• Recurrent Adenoid Cystic Carcinoma

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	Dana Farber Cancer Research Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California San Francisco Helen Diller Comprehensive Cancer Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Remix Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Secondary	Overall Response Rate (ORR)	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	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	18 months
Secondary	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
Secondary	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
Secondary	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	18 months
Secondary	Median Overall Survival (mOS)	mOS will be evaluated after treatment with REM-422	18 months
Secondary	Determine pharmacokinetic profile (Cmax) of REM-422	Measure Maximal concentration (Cmax) of REM-422	18 months
Secondary	Determine pharmacokinetic profile (Cmin) of REM-422	Measure Minimal concentration (Cmin) of REM-422	18 months
Secondary	Determine pharmacokinetic profile (Tmax) of REM-422	Measure Time to peak drug concentration (Tmax) of REM-422	18 months
Secondary	Determine pharmacokinetic profile (AUC) of REM-422	Measure Area Under the Curve (AUC) of REM-422	18 months