Risk-adapted Therapy for HPV-positive Oropharyngeal Cancer
This study, called ReACT 2.0, is for people with HPV-positive oropharyngeal (throat) cancer that is stage I, II, or III. It aims to find the best treatment by using HPV blood tests and other information like tumor stage and smoking history. You would receive either Pembroluzimab, a monoclonal antibody given through an IV, or standard observation. Researchers will look at how long people live without their cancer getting worse (progression-free survival) and how often serious side effects happen. The study is currently recruiting 116 participants.
- Study design
- This is a phase 2, randomized, open-label study involving 116 participants. Participants will be randomly assigned to receive either Pembroluzimab or observation.
- What's involved
- You would have screening for eligibility, in-clinic visits, urine tests, questionnaires, tumor assessments (X-ray, CT, MRI, or PET scans), blood tests (including NavDx TTMV-HPV DNA Testing), biobanking, ECGs, and tumor tissue biopsies. Treatment duration is up to 54 weeks.
- Compensation
- Not stated in the trial record.
- Follow-up
- Adverse events will be collected through 30 days following the end of treatment. Progression-free survival will be measured at 2 years.
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NCT07513324
Risk-adapted Therapy in HPV-positive Oropharyngeal Cancer Using Circulating Tumor (ct) HPV DNA Profiling (ReACT 2.0)
Not Yet Recruiting
PHASE2Ages 18+InterventionalTreatmentDana-Farber Cancer InstituteInvestigator-initiated
~116 participants
Updated 2026-06-09 on ClinicalTrials.gov
What's tested:PembroluzimabObservation
At a glance
Recruiting sites
0 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression-free Survival at 2 Years (PFS2)
Measured over 2 years
+1 more outcome measured
Conditions
Where it's being run
2 sites across 1 statesMassachusetts2
Study leadership
- Glenn Hanna, MD · PRINCIPAL_INVESTIGATOR · Dana-Farber Cancer Institute
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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:
Absolute neutrophil count (ANC) ≥1500/µL
Platelets \> 100,000/µL
Hemoglobin ≥9.0g./dL or ≥5.6 mmol/La
Creatinine OR Measured or calculated b creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Ability to understand and the willingness to sign a written informed consent document.
Participants or persons of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of therapy. Note: Contraception requirements should conform with CTFG guidelines. The pembrolizumab standard for use of highly effective contraceptive methods for POCBP is 120 days (5 half-lives) after the last dose. Abstaining from breastfeeding after study intervention is at least 5 half-lives or 120 days.
Exclusion
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.
What this trial measures
- Progression-free Survival at 2 Years (PFS2)2 years
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.
- Grade 3 or 4 Adverse Event (AE) RateTreatment duration is up to 54 weeks, and adverse events will be collected through 30 days following the end of treatment.
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.