To determine if it is feasible to use neoadjuvant immunotherapy (or immunotherapy plus chemotherapy) to reduce treatment intensity and improve long-term quality of life while maintaining very high cure rates.
Subjects must have pathologically confirmed HPV-positive head and neck squamous cell carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al89).
p16 IHC positivity is to be validated using an HPV nucleic acid based secondary assay (HPV ISH, HPV PCR, HPV cfDNA) before or during the neoadjuvant phase.*
HPV DNA ISH is acceptable if positive, however a negative HPV DNA ISH should be confirmed by HPV RNA ISH or other nucleic acid based method.
Unequivocal demonstration of distant metastases (M1 disease).
Unidentifiable/unknown primary site (neither imaging nor exam nor biopsy can identify the primary). Treating physicians should agree that the primary is sufficiently identified to proceed with clinical care/treatment (e.g. in the case of imaging localization, but absence of biopsy proven pathology)
Intercurrent medical illnesses which would impair subject tolerance to therapy or limit survival. Including but not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Once clinically stable, as defined by the PI, they are eligible.
Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns (please see above paragraph under inclusion criteria regarding WOCBP)
Parallel
Cemiplimab
DrugCemiplimab for 9 weeks +/- Carboplatin + Paclitaxel
2-year progression free survival rate
Change in Quality of life as measured by MD Anderson Dysphagia Inventory (MDADI)
The MD Anderson Dysphagia Inventory (MDADI) is a 20 item quality of life instrument specifically focusing on swallowing. The total score ranges from 20 to 100 with the higher score indicating higher level of function. Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree).
Change in quality of life as measured by the Sydney Swallow Questionnaire (SSQ).
The SSQ consists of 17 questions, (16 visual analogue scales (VAS) and one question scored on a Likert scale (0-5). The score for each VAS question is the distance in mm from the origin (left extremity) to the patient's mark on the visual analogue scale. The total score is calculated by summing the 16 individual VAS scores and the Likert scale (0-5) multiplied by 20. Thus converting the range of possible scores for Likert question from 0-5 to 0-100, consistent with the remaining 16 questions, to yield a total score out of a possible maximum of 1700. Higher scores indicate higher symptomatic severity of oral-pharyngeal dysphagia.
Change in swallow function as measured by the Sydney Swallow Questionnaire (SSQ).
Desirable swallowing function at 1 year for this study will be defined as SSQ ≤ 250 and MDADI ≥ 70
To determine 2-year overall survival (OS) for the entire cohort
OS will be estimated by Kaplan-Meier methodology and comparisons will be made using the log-rank test. OS is defined as the time between the date of registration and the date of death.
To determine 2-year rates of locoregional and distant control for the entire cohort
Locoregional and distant control will be assessed by immune response criteria using Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
Number of grade 3 toxicities
We will report the number of grade 3 toxicities using Common Terminology Criteria for Adverse Events (CTCAE).
Number of grade 4 toxicities
We will report the number of grade 4 toxicities using Common Terminology Criteria for Adverse Events (CTCAE).
Rate of Induction Tumor/HPV
To determine the rate of induction of tumor/HPV specific immune response (HPVFEST assay) after induction therapy
HPV ctDNA Clearance
This will be used to assess treatment efficacy (e.g. during cemiplimab neoadjuvant treatment +/- addition of chemotherapy), as well as a potential marker for early recurrence after definitive treatment.
To interrogate the immune micro-environment at baseline, and 3 weeks into induction therapy with cemiplimab and chemotherapy based on an on-treatment biopsy
Multicolor IF to assess changes in the immune microenvironment
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
