• Be able to provide informed consent.

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

• 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. Radiographic eligibility as determined by Central IUO assay.

• Biomarker eligibility as determined by central IUO assay.

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

• Tumor Tissue Requirements

• 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 the initiation of REM-422 unless medically contraindicated.

‣ Dose Expansion 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. An FFPE block can be submitted or a minimum of 15 fresh sectioned unstained slides.

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

• 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.

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

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

⁃ Participants of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.

⁃ 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.

⁃ 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.

⁃ Adequate bone marrow, organ function and laboratory parameters