Inclusion Criteria:

• Age ≥18 years

• Histologically Confirmed diagnosis of relapsed/metastatic oral cavity cancer

• Measurable or non-measurable disease is allowed

  • Measurable disease as defined by RECIST criteria

  • Non-measurable disease,NOTE: Other nonmeasurable lesions include clinically evident lesions not well visualized on imaging (e.g., oral cavity mass readily seen on physical exam but obscured on CT), dermal metastases, and bone metastases.

• Prior treatment: One of the following must be true:

  • (1) received standard 1st-line immunotherapy or chemo-immunotherapy OR

  • (2) unable to receive or refuse 1st-line therapy

• ECOG Performance Status (PS) 0, 1 or 2

• The following laboratory values obtained ≤15 days prior to registration:

  • Hemoglobin ≥9.0 g/dL

  • Absolute neutrophil count (ANC) ≥1500/mm3

  • Platelet count ≥100,000/mm3

  • Total bilirubin ≤1.5 x ULN

  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN (≤5 x ULN for patients with liver involvement)

  • PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy

  • Calculated creatinine clearance ≥45 ml/min per CKD-EPI Creatinine Equation Estimated creatinine clearance (Clcr) by the CKD-EPI Creatinine Equation (per National Kidney Foundation)

    • For females: eGFRcr = 142 x min(Scr/0.7, 1)-0.241 x max(Scr/0.7, 1)-1.200 x 0.9938Age x 1.012

    • For males: eGFRcr = 142 x min(Scr/0.7, 1)-0.241 x max(Scr/0.7, 1)-1.200 x 0.9938Age

• Negative pregnancy test done ≤8 days prior to registration, for persons of childbearing potential only

• Provide written informed consent

• Ability to complete questionnaire(s) by themselves or with assistance

• Ability to swallow pills

• Willing and able to adhere with the protocol schedule for the duration of the study including undergoing treatment, attending scheduled visits, and examinations.

Exclusion Criteria:

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown

  • Pregnant persons

  • Nursing persons

  • Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception

• Uncontrolled intercurrent illness including, but not limited to:

  • Myocardial infarction ≤ 6 months prior to registration

  • NYHA class III or IV heart failure

  • QTc prolongation more than 440 ms in males and 460 ms in females

  • Uncontrolled dysrhythmias or poorly controlled angina

  • History of serious ventricular arrhythmia (VT or VF) and/or factors that predispose to arrhythmia (e.g., heart failure, hypokalemia, family history of Long QT syndrome)

  • Ongoing or active infection requiring systemic treatment

  • Active gastrointestinal bleeding

  • Psychiatric illness/social situations that would limit compliance with study requirements

• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

• Known hepatitis

  • Exception: For patients with evidence of chronic hepatitis B virus infection the HepB viral load must be undetectable on suppressive therapy, if indicated, to be eligible.

  • Exception: Patients with a history of hepatitis C virus infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Other active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy. Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria. NOTE: Patients with secondary malignancy with life expectancy ≥2 years are eligible

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 04/30/2025. Questions regarding updates should be directed to the study team contact.