‣ Participants must meet the following eligibility criteria at the time of screening to be eligible to participate in the study:

‣ Eligibility Criteria

• Participants must have histologically confirmed adenoid cystic carcinoma (ACC) with evidence of recurrent, metastatic or advanced, incurable disease arising from any primary site

• Activating mutation in the NOTCH signaling pathway

• In Cohort 1 only, prior multitargeted VEGFR TKI or systemic therapy is permitted.

• In Cohort 2 only, no prior multitargeted VEGFR TKI therapy is permitted, but prior systemic chemotherapy as part of definitive or curative intent management is permitted.

• a. Any participant must obtain prior approval from insurance to reimburse for oral Lenvatinib, or off-label drug assistance to secure Lenvatinib for the duration of the study or agree to self-pay for oral Lenvatinib or obtain institutional commitment from the study site to provide Lenvatinib.

• Age 18 years or older

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

• Patients able and willing to swallow oral capsules or tablet medications.

• At least one measurable lesion (RECIST v1.1)

• Participant must have organ and marrow function as defined below within 14 days prior to study registration (ULN=upper limit of normal per institution):

• Absolute neutrophil count (ANC) ≥1.5 x 109/L Hemoglobin (Hgb) ≥9 g/dL (patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion).

• Platelet count ≥100 x 109/L (without transfusion within the last 5 days) Serum creatinine ≤1.5x ULN or serum creatinine clearance (CrCl) ≥50 mL/min (estimated by Cockcroft-Gault formula) Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3x ULN Total serum bilirubin ≤1.5x ULN (patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted).

⁃ Baseline proteinuria with a urinalysis or urine dipstick value of 2+ requires a spot urine protein/creatinine ratio of \<0.3 (or 24-hour urine collection protein value \<300 mg/g) in Cohort 2 only

⁃ Participants with treated brain or CNS metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no convincing evidence of progression and patients are neurologically stable with no new neurological deficits.

⁃ Female subjects of childbearing potential should have a negative serum pregnancy test within 7 days before start of study treatment.

⁃ Female and male subjects of childbearing potential must agree to use an adequate method of contraception to avoid pregnancy (with at least 99% certainty) from screening through 90-days or 3-months post-treatment completion (see Appendix B).

⁃ Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

⁃ Patients who received chemotherapy must have recovered (CTCAE grade ≤1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy. A washout period of at least 21 days is required between last chemotherapy dose and start of therapy (provided the patient did not receive radiotherapy).