Toripalimab in Combination With Standard Treatment for Human Papillomavirus (HPV) Positive Throat Cancer

Phase II Trial of Neoadjuvant Toripalimab in Combination With Chemotherapy Followed by Transoral Robotic Surgery or Risk/Response Stratified Chemoradiotherapy for Locoregional HPV16+ Oropharyngeal Cancer: TARGET HPV Cohort 2

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).

Study Overview

• Status: Recruiting
• Conditions: Oropharyngeal Cancer
• Intervention / Treatment: Drug: Toripalimab; Drug: Carboplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cancer Trials Intake; Phone Number: 1-855-702-8222; Email: cancerclinicaltrials@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medicine Comprehensive Cancer Center
      • Contact: Clinical Trials Intake; Phone Number: 855-702-8222; Email: cancerclinicaltrials@bsd.uchicago.edu
      • Principal Investigator: Ari Rosenberg
      • Contact: Ari Rosenberg; Email: arirosenberg@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

• HPV16 subtype demonstrated based on the following guidelines:

  • 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.
• Patients must be at least 18 years of age.
• Subjects with AJCC (8th edition, 2018) N1 (if solitary lymph node must be >=3cm), N2-N3 nodal disease or T3-T4 primary tumor (with any N).
• Measurable disease (either primary site and/or nodal disease) by RECIST 1.1 criteria.
• No previous radiation or chemotherapy for a head and neck cancer.
• No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual measurable disease is acceptable.) No surgical procedures or biopsies will occur after baseline scans are performed and measurable lesions are identified.
• ECOG performance status 0-1
• Normal Organ Function per protocol criteria
• Patients must be considered to be a candidate to receive cisplatin by the treating physician.
• Patients must sign a study-specific informed consent form prior to study entry. Patients should have the ability to understand and the willingness to sign a written informed consent document.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
• Women must not be breastfeeding.
• Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment.
• Men who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s).

Exclusion Criteria:

• 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).
• Subject with low risk N1 disease (defined as single lymph node <3cm)

• Active, known, or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy, with the exception of low-dose prednisone (<= 10mg or equivalent). The following are exceptions to these criteria:

  • Patients with vitiligo or alopecia.
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic treatment.
• Treatment with immunosuppressive or replacement medication:
• Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent), within 14 days of the first administration of study treatment. Note: inhaled or topical steroids and adrenal replacement in doses equivalent to > 10 mg/day prednisone are permitted in the absence of active autoimmune disease.
• Any chronic immunosuppressive medication within 6 months prior to the first administration of study treatment (unless agreed otherwise between the Sponsor and the Investigator on a case-by-case basis).
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Patients who have had a prior anaphylactic or other severe reaction to human immunoglobulin or antibody formulation administration.
• Herbal remedies with immune-stimulating properties or known to potentially interfere with major organ function within 28 days prior to the first dose of study treatment, unless agreed otherwise with the primary investigator.
• Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment as discussed above.
• Patients receiving other investigational agents.
• Prior systemic anti-cancer treatment within the last 8 weeks.
• 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 life expectancy in the subsequent 3 years without active treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has known active Hepatitis B or hepatitis C. If eradicated, patient is eligible.
• Has received a live vaccine within 28 days of planned start of study therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Toripalimab and Chemotherapy Treatment; Participants will receive toripalimab with neoadjuvant chemotherapy. After completion of the study treatment all patients will proceed with risk and response stratified locoregional therapy.

Drug: Toripalimab; Toripalimab 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).; Other Names: LOQTORZI; Drug: Carboplatin; Carboplatin will be given by Intravenous (IV) infusion once on Day 1 of each treatment cycle.; Drug: Paclitaxel; Paclitaxel will be given by Intravenous (IV) infusion once weekly for 9 weeks (except for Day 22 of cycle 1).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	After treatment completion (about 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	After treatment completion (about 3 months)
Progression Free Survival	Time to disease worsening will be calculated	5 years after treatment completion
Overall Survival	Time to death will be calculated	5 years after treatment completion
Locoregional Control	Time to local disease worsening will be calculated	5 years after treatment completion
Distant Control	Time to disease worsening or spreading to other parts of the body	5 years after treatment completion
Treatment adherence	Dose delays, dose reductions, and chemotherapy discontinuations during neoadjuvant treatment will be summarized by type, worst grade, and attribution.	After treatment completion (about 3 months)

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Ari Rosenberg, University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2033

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Oropharyngeal Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel; toripalimab
• Other Study ID Numbers: IRB25-1616

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No