Toripalimab in Combination with Cisplatin and Docetaxel for the Treatment of Locally Advanced Stage III or Non-metastatic Stage IV Head and Neck Squamous Cell Carcinoma

Inclusion Criteria

• Participants must have a new diagnosis of histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, sinonasal cavities or unknown primary HNSCC.
• Participants with human papillomavirus (HPV)-independent squamous cell carcinoma (SCC) or HNSCC or other head and neck subsites must have stage III or non-metastatic stage IV at the time of diagnosis. Participants with HPV-associated oropharynx SCC must have stage II or stage III disease.
• Participants must be determined by the investigator to be candidates for induction systemic therapy due to reasons such as the extent of primary tumor at the time of diagnosis, rate of progression, symptom burden or potential benefit of cytoreduction prior to definitive local therapy.
• Combined positive score (CPS) ≥ 1%
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of toripalimab in combination with cisplatin and docetaxel in participants < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy of greater than 12 weeks.
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count ≥ 1500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 2 institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine (ALT)(serum glutamic pyruvate transaminase [SGPT]) ≤ 2 × institutional ULN
• Creatinine ≤ 2 x institutional ULN OR glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m^2
• 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.
• Because immunotherapy agents as well as cisplatin and docetaxel are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of toripalimab administration.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Diagnosis of Epstein-Barr virus (EBV)-associated nasopharynx squamous cell carcinoma
• Strong clinical suspicion or histologic confirmation of cutaneous squamous cell carcinoma
• Histology other than squamous cell carcinoma.
• Proven distant metastases (below the clavicle) by clinical or radiographic measures.
• Prior radiotherapy to the head and/or neck with the exception of radiation for cutaneous malignancies involving radiation fields that do not overlap with areas of current disease involvement.
• Pre-existing peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher
• Participants who are receiving any other investigational agents for this condition.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to toripalimab, cisplatin or docetaxel.
• An autoimmune condition requiring treatment with systemic corticosteroids within the past 30 days. Long-term steroid replacement for patients with adrenal insufficiency is allowed.
• Any second malignancy that required antineoplastic therapy in the previous 6 months.
• Participants receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP450 enzyme(s) are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant 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 participant is considering a new over-the-counter medicine or herbal product.
• Pregnant women are excluded from this study because toripalimab, cisplatin and docetaxel have 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 toripalimab, cisplatin and docetaxel, breastfeeding should be discontinued if the mother is treated with toripalimab. These potential risks may also apply to other agents used in this study.