A Study Comparing Two Immunotherapy Options for Human Papillomavirus Positive HPV-Positive Head and Neck Cancer After Treatment

NCT07179315 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB25-0846
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if the combination of cemiplimab and fianlimab can improve outcomes compared to cemiplimab alone in adults with Human Papillomavirus Positive HPV-positive head and neck cancer who have detectable minimal-residual disease after definitive treatment. The main question(s) it aims to answer are:

• Does combining cemiplimab with fianlimab provide better results in preventing cancer recurrence than cemiplimab alone?
• Is the combination treatment safe and well-tolerated by patients? Researchers will compare the group receiving cemiplimab alone to the group receiving the combination of cemiplimab and fianlimab to see if the combination leads to improved treatment outcomes, such as better disease control and longer survival. Participants will:
• Receive either cemiplimab alone or a combination of cemiplimab and fianlimab.
• Attend regular follow-up visits for monitoring of treatment efficacy and side effects.
• Undergo assessments to measure disease progression and response to treatment.

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Assess improved recurrence free survival in patients

  The primary objective is to assess whether cemiplimab with fianlimab compared to cemiplimab alone will result in improved recurrence free survival in patients with detectable MRD after definitive treatment for Human Papillomavirus Positive HPV(+) head and neck cancer.

  assessed up to 5 years after enrollment completed

Secondary Outcomes (4)

• Recurrence free survival (RFS) improvement of cemiplimab with or without fianlimab

  assessed up to 5 years after enrollment completed

• Assess improved circulating tumor Human Papillomavirus Positive HPV-DNA clearance rate

  2 years after start of study

• Compare patterns of disease recurrence and survival

  assessed up to 5 years after enrollment completed

• Assess safety and tolerability of cemiplimab plus fianlimab

  assessed up to 5 years after enrollment completed

Study Arms (2)

two monoclonal antibodies together for 1 year

EXPERIMENTAL

This arm is assigned to intervention 1

Drug: cemiplimab+fianlimab

One monoclonal antibody alone for 1 year

EXPERIMENTAL

This arm is assigned to intervention 2

Drug: Cemiplimab

Interventions

cemiplimab+fianlimab DRUG

Fianlimab 1600 mg + Cemiplimab 350 mg FDC

two monoclonal antibodies together for 1 year

Cemiplimab DRUG

350 mg

One monoclonal antibody alone for 1 year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have history of histologically confirmed squamous cell carcinoma of the oropharynx.
• Must be HPV positive; testing must be compliant with meeting any one or more of the following criteria:
• p16 IHC positivity (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al.37).
• HPV PCR positivity.
• HPV in situ hybridization (ISH) positivity.
• Completed curative intent therapy. Acceptable curative intent therapies may include any combination of surgery, radiotherapy, and/or chemotherapy is eligible. Curative intent therapy must be completed at least 1 month prior to enrollment.
• Any T or N stage at time of initial diagnosis is permitted, including patients with unknown primary, supraclavicular or mediastinal nodal involvement at the time of curative intent treatment.
• Detectable ctHPVDNA in plasma confirmed by NavDx prior to enrollment based on the clinically validated circulating tumor-tissue-modified HPV (TTMV®) DNA plasma assay. Patients with detectable ctHPVDNA in plasma from other commercially available CLIA-certified assays are also eligible, however a positive NavDx assay is required and will be obtained during screening.
• PD-L1 biomarker analysis from a core or excisional biopsy must be performed by IHC using the 22C3 antibody and a CPS score must be calculated for stratification. If unavailable, result from a fine-needle aspirate can also be acceptable. Local testing is acceptable.
• No definitive clinical or radiographic evidence of disease evaluated by clinical examination and cross-sectional imaging and/or PET imaging prior to randomization. Patients with equivocal results on imaging are eligible.
• Patients must be willing and able to provide written informed consent for the trial.
• Patients must be at least 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the ECOG Performance Scale. An ECOG performance status of 2 is acceptable if the patient was ECOG 0/1 prior to curative intent therapy and is in the midst of recovery from curative intent therapy.
• Demonstrate reasonable organ function as defined below in Table below
• System and Laboratory Value

You may not qualify if:

• Clinical or radiographic evidence of gross disease that warrants further curative intent therapy or systemic/palliative therapy (e.g. platinum containing chemotherapy, cetuximab, pembrolizumab).
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10mg of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy or typical side effects from radiotherapy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Patients who are receiving any other investigational agents.
• 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 (e.g. low grade prostate cancer in absence of therapy).
• History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
• Active infection requiring therapy.
• Uncontrolled infection with HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection.
• Notes:
• Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
• Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
• Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

Sponsors & Collaborators

• University of Chicago: lead

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Ari Rosenberg

  University of Chicago

  STUDY CHAIR

Central Study Contacts

Cancer Center Intake

CONTACT

1-855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: September 17, 2025
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03