This is a single-center phase 2 study of to test how well the combination of toripalimab with chemotherapy followed by TORS or risk and response stratified de-escalated (chemo)radiotherapy works in patients with in HPV16+ locoregionally advanced oropharyngeal cancer (OPC).
Subjects must have pathologically confirmed HPV16-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 al72).
HPV PCR must demonstrate HPV16 subtype.
Following p16 IHC positivity, HPV16 is to be demonstrated using HPV PCR which is anticipated to result prior to cycle 1 day 15.
Unequivocal demonstration of distant metastatic disease (M1 disease).
Non-HPV16 subtype.
Unidentifiable primary site.
Intercurrent medical illnesses that impairs the patient's tolerance to therapy or limits survival. This includes but is 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. Patients with clinically stable and/or chronically managed medical illnesses that are not symptomatic and/or are not expected to impact treatment on protocol are still eligible (conditions to be reviewed by the PI to confirm eligibility).
Single group
Toripalimab
DrugToripalimab will be given by Intravenous (IV) infusion once on Day 1 of each treatment cycle. Up to 3 cycles of treatment will be given. The first treatment cycle will last 28 days (4 weeks). Cycles 2 and 3 will last 21 days (3 weeks).
Carboplatin
DrugCarboplatin will be given by Intravenous (IV) infusion once on Day 1 of each treatment cycle.
Paclitaxel
DrugPaclitaxel will be given by Intravenous (IV) infusion once weekly for 9 weeks (except for Day 22 of cycle 1).
Deep Response Rate (DRR) with toripalimab + chemotherapy
The proportion of patients who attain a deep response following neoadjuvant toriaplimab + chemotherapy. DDR is defined as tumor shrinkage by 50% or more.
Side effects of toripalimab + chemotherapy
Summary of side effects seen by types and severity and relatedness to study treatment as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Progression Free Survival
Time to disease worsening will be calculated
Overall Survival
Time to death will be calculated
Locoregional Control
Time to local disease worsening will be calculated
Click on the lead sponsor to view all of their trials.
