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

Inclusion Criteria:

1. Be able to provide informed consent.

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

3. Disease criteria:

4. Histologically confirmed ACC, any site of origin.

5. Have locally advanced or metastatic ACC.

6. Dose Escalation phase ONLY: Evidence of radiographic progression and/or signsand symptoms associated with their disease (eg, pain, dyspnea, reducedperformance status). Participants who have stable disease while being treatedwith another agent that is not tolerated are eligible after the appropriatewashout period.

7. Dose Expansion phase ONLY:

• Measurable disease at the time of enrollment. At least 1 measurable lesionaccording to RECIST v1.1 criteria. Participants must have radiographicevidence of disease progression by RECIST v1.1 criteria ≤ 6 months priorto study enrollment. Radiographic eligibility as determined by Central IUOassay.
• Biomarker eligibility as determined by central IUO assay.

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

5. Tumor Tissue Requirements Dose Escalation Phase ONLY: be able to provide during Screening a tissue specimen ofeither a fresh biopsy of a non-target lesion or an archival tumor sample obtainedwithin the last 6 years. A formalin-fixed paraffin-embedded (FFPE) block can besubmitted or a minimum of 15 freshly sectioned unstained slides.

6. Agree to an on-treatment biopsy to be obtained ~4-8 weeks after the initiationof REM-422 unless medically contraindicated.

7. Dose Expansion phase ONLY: be able to provide, during Pre-Screening, a tissuespecimen of either a fresh biopsy of non-targetable lesion or an archival tumorsample obtained within the last 6 years. An FFPE block can be submitted or aminimum of 15 fresh sectioned unstained slides.

8. At least 3 weeks since prior systemic non-investigational therapy at the time ofstart of REM- 422.

9. Toxicities from prior therapy must be stable or recovered to ≤ Grade 1. Note: Stablechronic and clinically non-significant conditions (≤ Grade 2) that are not expectedto resolve are exceptions (eg, neuropathy, myalgia, alopecia, prior therapy-relatedendocrinopathies, etc.), and patients with these conditions may enroll.

10. Participants must be able to swallow and retain oral medications.

11. Oxygen saturation > 92% on room air or up to 2 L/min supplemental oxygen by nasalcannula with ≤ Grade 1 dyspnea.

12. Participants of childbearing potential (POCBP) must have a negative serum beta-humanchorionic gonadotropin test result.

13. Participants Of Child Bearing Potential must agree to use acceptable, effectivemethods of contraception as outlined in Appendix 1 and not donate ova from Screeninguntil 6 months after discontinuation of REM- 422. Women who have undergone surgicalor ablative sterilization or who have been postmenopausal for ≥ 2 years are notconsidered to be of childbearing potential.

14. Men must agree to use acceptable, effective methods of contraception and must agreenot to donate sperm from the start of receiving REM-422 until 6 months afterdiscontinuation of REM-422.

15. Adequate bone marrow, organ function and laboratory parameters

Exclusion Criteria:

1. Known hypersensitivity or contraindication to any component of REM-422 or to drugschemically 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 areexcluded (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 ofprednisone equivalent. Topical or inhaled corticosteroids with minimal systemicabsorption may enroll and continue minimal corticosteroids if the participant is ona 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 7days prior to the initiation of REM-422 administration or during the study

10. Pregnancy or participants planning to become pregnant during the duration of thestudy, or lactation.

11. Participants with malabsorption syndrome, a disease significantly affectinggastrointestinal 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 asthe pleural cavity, peritoneum, meninges, or surgical procedures requiring generalanesthesia) < 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) ≤ 2years of enrollment, except curatively treated malignancies including basal orsquamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in situ ofthe cervix.

19. Participants receiving any other investigational treatment for any indication ≤ 3weeks prior to enrollment.

20. Unwillingness or inability to follow protocol requirements.

21. Any condition that, in the opinion of the Investigator, would interfere withevaluation of REM-422 or interpretation of the participant's safety or studyresults.