Risk-adapted Therapy in HPV-positive Oropharyngeal Cancer Using Circulating Tumor (ct) HPV DNA Profiling (ReACT 2.0)

NCT07513324 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-742
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess risk for HPV driven oropharyngeal cancers by using HPV blood tests and clinical features (such as tumor stage and smoking status) to determine appropriate treatment to improve survival outcomes in participants with stage I, II, or III, HPV-associated oropharyngeal (tongue base or tonsil) squamous cell carcinoma,.

Conditions

Oropharyngeal Squamous Cell Carcinoma; HPV-positive Oropharyngeal Squamous Cell Carcinoma

Keywords

HPV-positive oropharyngeal squamous cell carcinoma; Oropharyngeal squamous cell carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival at 2 Years (PFS2)

  PFS2 is the percent probability estimate at 2 years based on the Kaplan-Meier method. PFS is defined as the time from the date of randomization to first invasive local, regional, distant progression, invasive second head and neck primary, or death due to any cause. Participants alive without progression are censored at date of last disease evaluation. Progression should be confirmed by biopsy or lymph node removal when feasible, but may also be determined based on clinical or pathologic evidence at the discretion of the treating investigator.

  2 years

• Grade 3 or 4 Adverse Event (AE) Rate

  Grade 3 or 4 AE rate is defined as the proportion of participants who experience grade 3 or 4 adverse events during study treatment. AEs are summarized and graded based on CTCAE 5.0.

  Treatment duration is up to 54 weeks, and adverse events will be collected through 30 days following the end of treatment.

Secondary Outcomes (3)

• Median Progression-free Survival (PFS)

  Tumor assessments will be performed every 12 weeks (±2 weeks) for up to 2 years following randomization.

• Median Overall Survival (OS)

  Survival will be monitored every 12 weeks (±2 weeks) for up to 2 years following randomization.

• Median Distant Metastatic-free Survival (DMFS)

  Tumor assessments will be performed every 12 weeks (±2 weeks) for up to 2 years following randomization.

Study Arms (2)

Adjuvant Pembroluzimab

EXPERIMENTAL

* Cycle 1 through Cycle 9 (42-day cycles) * Days 1-378: Predetermined dose of Pembrolizumab once every 6 weeks, up to 9 cycles * Follow up for up to 2 years

Drug: Pembroluzimab

Observation

ACTIVE COMPARATOR

Cycle 1 through Cycle 9 (42-day cycles) Days 1-378: Standard of care observation Device: NavDx® TTMV-HPV DNA testing (used for risk stratification and treatment assignment) Follow up for up to 2 years

Other: Observation

Interventions

Pembroluzimab DRUG

monoclonal antibody, single-dose vial via intravenous (through the arm) infusion, per protocol

Also known as: Keytruda, MK-3475

Adjuvant Pembroluzimab

Observation OTHER

Standard of care observation

Observation

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed, stage I, II, or III, HPV-associated oropharyngeal (tongue base or tonsil) squamous cell carcinoma, as defined by 2017 American Joint Committee on Cancer (AJCC), 8th edition staging. Participants with HPV-associated disease of unknown primary (cT0) are eligible.
• Participants who undergo upfront surgery are permitted to enroll if their post-operative pathology necessitates that they receive adjuvant therapy.
• Participants who undergo upfront induction chemotherapy with platinum-based therapy are eligible if they have less than a complete clinical or radiologic response to induction as judged by the treating investigator(s).
• Participants with locoregionally recurrent disease are eligible if they completed definitive or curative-intent treatment and meet criteria 3.1, 6e below.
• HPV status should be confirmed on tissue biopsy or cytologic sample by any of the following: (a) IHC staining for p16 with ≥70% expression, and/or (b) DNA testing (PCR or ISH) for high-risk subtypes 16, 18, 31, 33, or 35.
• Tumor tissue available for PD-L1 CPS testing.
• Age 18 years or older at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Intermediate or high-risk HPV+ disease defined by any one of the following:
• TTMV-HPV DNA score \>200 at baseline and failure to clear by \>95% by week 4-5 of treatment
• undetectable or low (≤200) TTMV-HPV DNA at baseline prior to treatment with clinical or pathologic T3-4 or N2-3 disease
• known HPV subtypes 18, 31, 33, or 35 (but excluding cT1-2N0 participants)
• known N3 disease or fixed neck nodes as judged by the treating investigator(s)
• any stage disease with known detectable TTMV-HPV DNA 6 weeks or onward from completion of definitive or curative-intent therapy without clinical or radiographic disease and with no additional intervening therapy administered.
• Participants should have adequate organ and marrow function to receive adjuvant immunotherapy as outlined below:

You may not qualify if:

• Participants with AJCC 2017 8th edition stage IV (M1, metastatic) disease.
• Pregnant or lactating women.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or another stimulatory or co-inhibitory T-cell receptor treatment.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of pembrolizumab.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days of first pembrolizumab dosing.
• Has 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. levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Participants with a history of allogeneic tissue/solid organ transplant are excluded.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of uncontrolled human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority. Well-controlled typically includes a CD4+ T-cell count ≥350 cells/mm3 at the time of screening and achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.
• Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• 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, and low-risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease is permitted if chance of recurrence is thought to be low (in discussion with the Sponsor-investigator).
• ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• b Creatinine clearance (CrCl) should be calculated per institutional standard.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Observation

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Glenn Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn Hanna, MD

CONTACT

617-632-3779; Gjhanna@partners.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 7, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (2)