Dosing Study of Radiation Combined With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Cancer

* Patients who have had chemotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.

* Patients may not be receiving any other investigational agents.

* History of allergic reactions attributed to compounds of similar chemical composition or excipients used in the study.

* Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).

* Note: Patients who are currently or have recently been on any of the following corticosteroid regimens are not excluded:

Adrenal replacement corticosteroid (dose ≤ 10 mg daily of prednisone or equivalent)

Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption

Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a nonautoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)

* Has hypersensitivity to tislelizumab, pamiparib, or any other drug used in this protocol.

* Has a known history of active tuberculosis (Bacillus Tuberculosis infection)

* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy), or prior history of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS).

* Has active autoimmune disease that has required systemic treatment in the past year (i.e. with use of steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment.

* Has known history of, or any evidence of active interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.

* Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

* Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). However, if eradicated subject is eligible.

* Has received a live vaccine within 28 days of planned start of study therapy.

o Note: Vaccines for COVID-19 are allowed except for any live vaccine that may be developed. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed within 28 days prior to initiation of treatment. Vaccines should not be given during the chemo-radiation phase until marrow function has normalized as vaccines may not be efficacious during periods of marrow suppression.

* Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

* Patients receiving any medications or substances that are known to be strong CYP3A inducers (eg. avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampin/ rifampicin) are ineligible. Patients receiving herbal remedies/medicines such as St. John's Wort (Hypericum perforatum) are also ineligible. See Sections 5.5.2 and 5.5.3 for prohibited medications on study.

Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.

Pregnant women are excluded from this study because pamiparib is a PARP inhibitor and tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pamiparib and tislelizumab, breastfeeding should be discontinued if the mother is treated with pamiparib and tislelizumab.

HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pamiparib and tislelizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

Disease/procedure significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastrointestinal perforation or fistulae. Note: Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (assuming no drug interaction potential).

What this study is about