Inclusion Criteria:

- Patient (or a legally authorized representative) must understand and voluntarily
sign informed consent prior to any study-related assessments/procedures being
conducted.

- Must be able and willing to comply with the study visit schedule and protocol
requirements.

- Must have sufficient archived tumor tissue available for p16 immunohistochemistry
(IHC) staining if the status is unknown. HPV status determined by HPV DNA
sequencing, HPV DNA/RNA in situ hybridization, or equivalent assays using tumor
tissue or cell free HPV DNA testing or equivalent using blood-based assays are also
acceptable. If there is a discrepancy between p16 IHC and HPV detection assay
results, HPV detection assay result will be used.

- Must have sufficient archived tumor tissue available for OncoSignature
determination. The tumor tissue must be less than 3 months old from the enrollment
date. There should not be any intervening systemic therapy from the date of tumor
tissue collection. If not, patient must agree to a fresh tumor biopsy before
starting the treatments.

- Must agree to a biopsy after the lead-in LDG infusion and at the time of disease
progression (or end of treatment if applicable).

- Must have R/M HNSCC including oral cavity, oropharynx, larynx, and hypopharynx.
Patients with p16-positive or HPV-positive unknown primary of head and neck are
eligible.

- Must have been treated with one prior line of PD-1/PD-L1 inhibitor with/without
chemotherapy. Patients who are immunotherapy ineligible due to history of autoimmune
disease or steroid requirement (prednisone >10mg per day or equivalent) are allowed
to enroll without the one prior line of PD-1/PD-L1 inhibitor with/without
chemotherapy. There is no limitation on the number of prior therapies received in
the R/M setting.

- Must have at least one measurable lesion as defined by RECIST v1.1.

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

- Must meet the laboratory criteria outlined in the protocol. Blood transfusion and/or
blood product support are allowed.

- Patients of childbearing potential and patients whose sexual partners are of
childbearing potential must be willing to practice an approved method of highly
effective birth control with their partners starting at the time of informed consent
and for 1 year after the completion of the study treatment regimen.

Exclusion Criteria:

- Patients should not have any prior systemic therapy for 4 weeks from the time of the
study treatment.

- Patients should not have any palliative radiation therapy for 2 weeks from the time
of the study treatment. Palliative radiation therapy is permitted during the study
treatment if it does not involve target lesions.

- Patients with prior therapy-related toxicities Grade >1 per National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0;
except for dysphagia, alopecia, or vitiligo. Immunotherapy-related endocrinopathies
stable for at least 1 month, and controlled with hormonal replacement, are not
excluded. Grade 2 neuropathy stable for at least 2 weeks and controlled with
supportive care medications are not excluded.

- Patients with symptomatic and/or untreated brain metastases (of any size and any
number). Patients with definitively treated brain metastases may be eligible, must
be stable for at least 2 weeks and must be asymptomatic with or without prednisone
<10mg (or equivalent).

- Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New
York Heart Association (NYHA) Class 2 or higher.

- Patients with cardiovascular disease defined as: A) Uncontrolled hypertension
defined as blood pressure > 160/90 mmHg at Screening confirmed by repeat (medication
permitted). B) History of torsades de pointes, significant Screening
electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances,
unstable cardiac arrhythmia requiring medication, pathologic symptomatic
bradycardia, left bundle branch block, second degree atrioventricular (AV) block
type II, third degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not
amenable to correction, congenital long QT syndrome, prolonged QT interval due to
medications, corrected QT (QTc) > 450 msec (for men) or > 470 msec (for women). C)
Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo,
2019), unstable angina, myocardial infarction, severe cardiovascular disease
(ejection fraction < 20%, transient ischemic attack, or cerebrovascular accident
within 6 months of Day 1).

- Patients who have had another primary malignancy within the previous 3 years (except
for those who do not require treatment or have been curatively treated >1 year ago,
and in the judgment of the Investigator, do not pose a significant risk of
recurrence; including, but not limited to, non-melanoma skin cancer, ductal
carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS], or prostate cancer
Gleason score ≤6.).

- Patients who are of the following protected classes will be excluded: Pregnant,
parturient, or breastfeeding women. Persons who are hospitalized without consent or
those deprived of liberty because of a judiciary or administrative decision.
Patients with a legal protection measure or a person who cannot express his/her
consent and for whom a legally authorized representative is not available.

- Patients in emergency situations who cannot consent to the study and for whom a
legally authorized representative is not available.