Head and Neck CancerPhase 2NCT02841748
A Randomized, Double-Blind Phase II Study of Adjuvant Pembrolizumab Versus Placebo in Head and Neck Cancers at High Risk for Recurrence- the PATHWay Study
A Phase 2 study testing Pembrolizumab in people with Head and Neck Cancer and Squamous Cell Carcinoma of the Head and Neck, run by University of Chicago at 4 sites in United States.
Trial summary
A placebo-controlled, randomized study using adjuvant pembrolizumab treatment for one year in order to potentially improve progression free survival in a squamous cell carcinoma of the head and neck cohort at high-risk for recurrence. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 4 sitesUnited States
- Study dates
- 10 May 2017to 23 Oct 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed head and neck cancer (Squamous cell histology as well as HPV+ and/or EBV+ head and neck tumors), Stages IVA, IVB, and select cases of Stage III.
- HPV status required prior to randomization for oropharyngeal primary tumors
- EBV status is required prior to randomization for nasopharyngeal primary tumors
- Completed curative intent therapy, without additional standard of care curative intent therapy feasible within 20 weeks prior to study enrollment
- After prior curative intent treatment for HNC have estimated risk of recurrence ≥ 40-50% and fall into one of the below categories (A, OR B, OR C, OR D, OR E). While exact estimation of the risk of recurrence can be difficult the following categories will be included reflecting patients at substantial risk for tumor recurrence or already with early evidence of recurrence:
- A: Any of the below HNC patients are eligible for adjuvant treatment on this protocol AFTER completion of curative intent therapy:
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- HPV(-) HNC: N2C, N3, bulky N2B disease (≥ 5cm LN/tumor conglomerate).
- HPV(+) HNC: N2C, N3, AND ≥ 10 pack years of tobacco use
- HPV(+) HNC with multilevel nodal involvement, AND bulky N2B disease (≥ 5cm LN/tumor conglomerate), AND ≥ 10 pack years of tobacco use
- EBV(+) NPC may be eligible if other criteria under A, or alternative criteria B, or C, or D, or E are met.
- HNC with supraclavicular or mediastinal nodal involvement (any HPV or EPV status ) at time of curative intent treatment and were treated as part of curative intent therapy
- Residual mass in area of prior tumor that on biopsy does not show residual tumor, is equivocal/not highly-suspicious on imaging but remains of concern, requires close follow-up AND is not resected/amenable to resection OR immediate palliative treatment.
- Non-responders to induction chemotherapy (PD on induction, or lack of tumor shrinkage (< 15% per RECIST)
- Interrupted treatment course or lower than intended radiation dose - i.e. interruption of radiation by ≥ 3 weeks (cumulative), or delivery of ≤ 50 Gy as part of a radiation based treatment (that was NOT a de-escalation approach).
- B: Patient treated with salvage treatment (i.e. salvage surgery or re-irradiation) for residual or recurrent tumor after prior radiation based therapy (either HPV+ or HPV- or EBV+) AND not a candidate for additional curative intent therapy (for various reasons including poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc). Positive margins or residual tumor may still be acceptable (see D)). Patients should also not be appropriate for systemic palliative therapy (e.g. in the case of overt disease).
- C: Metastases or indeterminate distant lesions that are not appropriate for either local radiation/SBRT treatment and also not appropriate for initiation of palliative system therapy (e.g. in the setting of overt metastatic disease). Such lesions should be negative/equivocal by PET imaging and if amenable negative by biopsy, but remain of concern and require close follow-up
- D: Oligometastatic disease treated with SBRT or other curative-intent therapy (e.g. surgery or RFA, etc) for oligometastatic disease.
- E: Microscopic or very low volume residual tumor after surgery or radiation based treatment (including salvage treatment or SBRT for oligometastatic disease), AND not a candidate for either additional curative intent therapy (for various reasons including feasibility, poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc) AND also not a candidate for systemic palliative therapy (for various reasons including microscopic/non-(RECIST) measurable low volume disease). Very low volume disease is defined as non-RECIST measurable).
- F: Patients with multiple recurrences or multiple primaries: specifically patients who had malignant or pre-malignant tumors/changes (with severe dysplasia present), who have undergone surgery ≥ 2 times, and currently do not have an indication for additional (adjuvant) treatment such as radiation, or surgery, or other treatment. This may include multiple recurrences/incidences of early stage tumors or premalignant lesions, however at least one lesion needs to show squamous cell carcinoma on pathology.
- NOTE: There may be additional scenarios for patients that are considered very high risk for disease recurrence and not appropriate for either curative or standard of care palliative therapy. Such patients can be considered for enrollment after discussion and approval by the PI and/or co-PI.
- Availability of tumor tissue (≥ 10 slides) for PD-L1, gene expression profiling (GEP), and additional testing.
- Be willing and able to provide written informed consent/assent for the trial.
- Be 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, all screening labs should be performed within 10 days of treatment initiation.
- 9. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- 10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- 11. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Has hypersensitivity to pembrolizumab or any of its excipients.
- 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.
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- 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.
- 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 live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy).
- Has known active (=growing) central nervous system (CNS) metastases and/or carcinomatous meningitis. Radiation or resected brain metastasis are acceptable if clinically stable.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed within 30 days prior to initiation of treatment
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago Medical Center
Chicago, Illinois, 60637
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Randomized, Double-blind Phase II Study of Adjuvant Pembrolizumab Versus Placebo in Head and Neck Cancers at High Risk for Recurrence - the PATHWay Study.
A placebo-controlled, randomized study using adjuvant pembrolizumab treatment for one year in order to potentially improve progression free survival in a squamous cell carcinoma of the head and neck cohort at high-risk for recurrence.
Read the detailed description
This is a multicenter, randomized, placebo-controlled, double blind Phase II clinical trial of pembrolizumab vs. placebo. Patients will be randomized after the completion of curative intent therapy. The primary endpoint is progression-free survival (PFS).
- Being tested
- Pembrolizumab, Placebo
- Keywords
- Pembrolizumab, HNSCC
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
200mg, every three weeks, iv, x 1 year
PlaceboDrug
iv, every three weeks, x 1 year
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | 200mg, every three weeks, iv, x 1 year Receives: Drug: Pembrolizumab |
| Placebo | Experimental | iv, every 3 weeks, x 1 year Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Time from randomization to disease progression or death from any cause.
Measured: 2 years (PFS at 2 years)
Secondary outcomes (5)
Progression Free Survival (PFS) in Gene Expression Profile (GEP) Positive Patients
Time from randomization to disease progression or death from any cause.
Measured: 2 years (PFS at 2 years)
Progression Free Survival (PFS) in PD-L1 >=10% Positive Patients
Time from randomization to disease progression or death from any cause.
Measured: 2 years (PFS at 2 years)
Overall Survival
Time from randomization to death from any cause
Measured: 2 years (OS at 2 years)
Overall Survival (OS) in Gene Expression Profile (GEP) Positive Patients
Time from randomization to death from any cause.
Measured: 2 years (OS at 2 years)
Overall Survival (OS) in PD-L1 >=10% Positive Patients
Time from randomization to death from any cause.
Measured: 2 years (OS at 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study start10 May 2017
- Primary completion11 Feb 2025
- Study completion23 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexander Pearson, M.D., Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02841748
- Sponsor's protocol ID
- IRB15-1632
- Status last verified
- May 2026
- First submitted
- 20 Jul 2016
- Last updated
- 13 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind Phase II Study of Adjuvant Pembrolizumab Versus Placebo in Head and Neck Cancers at High Risk for Recurrence - the PATHWay Study.
- ClinicalTrials.gov ID
- NCT02841748
- Acronym / sponsor ID
- IRB15-1632
- Keywords
- Pembrolizumab, HNSCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 10 May 2017 (actual)
- Primary completion
- 11 Feb 2025 (actual)
- Study completion
- 23 Oct 2025 (actual)
- First posted
- 22 Jul 2016 (estimated)
- Results
- Posted 13 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A placebo-controlled, randomized study using adjuvant pembrolizumab treatment for one year in order to potentially improve progression free survival in a squamous cell carcinoma of the head and neck cohort at high-risk for recurrence.
Detailed description
This is a multicenter, randomized, placebo-controlled, double blind Phase II clinical trial of pembrolizumab vs. placebo. Patients will be randomized after the completion of curative intent therapy. The primary endpoint is progression-free survival (PFS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: Pembrolizumab200mg, every three weeks, iv, x 1 year |
| Placebo | Experimental | Drug: Placeboiv, every 3 weeks, x 1 year |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients must have histologically confirmed head and neck cancer (Squamous cell histology as well as HPV+ and/or EBV+ head and neck tumors), Stages IVA, IVB, and select cases of Stage III.
- Completed curative intent therapy, without additional standard of care curative intent therapy feasible within 20 weeks prior to study enrollment
- After prior curative intent treatment for HNC have estimated risk of recurrence ≥ 40-50% and fall into one of the below categories (A, OR B, OR C, OR D, OR E). While exact estimation of the risk of recurrence can be difficult the following categories will be included reflecting patients at substantial risk for tumor recurrence or already with early evidence of recurrence:
- HPV(-) HNC: N2C, N3, bulky N2B disease (≥ 5cm LN/tumor conglomerate).
- HPV(+) HNC: N2C, N3, AND ≥ 10 pack years of tobacco use
Key exclusion criteria (20 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Has hypersensitivity to pembrolizumab or any of its excipients.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab200mg, every three weeks, iv, x 1 year | Drug | Pembrolizumab |
| Placeboiv, every three weeks, x 1 year | Drug | Placebo |
Primary outcome
Progression Free Survival (PFS)
Time frame: 2 years (PFS at 2 years)
Time from randomization to disease progression or death from any cause.
5 secondary outcomes
Progression Free Survival (PFS) in Gene Expression Profile (GEP) Positive Patients
Time frame: 2 years (PFS at 2 years)
Progression Free Survival (PFS) in PD-L1 >=10% Positive Patients
Time frame: 2 years (PFS at 2 years)
Overall Survival
Time frame: 2 years (OS at 2 years)
Overall Survival (OS) in Gene Expression Profile (GEP) Positive Patients
Time frame: 2 years (OS at 2 years)
Overall Survival (OS) in PD-L1 >=10% Positive Patients
Time frame: 2 years (OS at 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Pearson, M.D. principal investigator
University of Chicago
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Head and Neck Cancer and Squamous Cell Carcinoma of the Head and Neck, run by University of Chicago at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: 2 years (PFS at 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.