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Head and Neck CancerPhase 2NCT03085719

Targeting PD-1 Therapy Resistance With Focused High or High and Low Dose Radiation in SCCHN

A Phase 2 study testing Pembrolizumab and Radiation in people with Head and Neck Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This research study is studying immunotherapy in combination with radiation therapy as a possible treatment for head \& neck cancer that has worsened or spread to another organ or part of your body. The immunotherapy involved in this study is: MK-3475 (pembrolizumab or KEYTRUDA). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
Pembrolizumab and Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
30 Jun 2017to 31 Oct 2027
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

  • Pathologically confirmed squamous cell carcinoma of the head and neck with evidence of metastatic disease considered incurable by local therapies. Patients without pathologic or cytologic evidence of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
  • Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy, or have stable disease on prior PD-1 therapy (at least 6 doses) and/or have been deemed not to derive clinical benefit from PD-1 directed treatment.
  • Patients must have least 3 measurable non-CNS based lesions that have not previously been irradiated. Palliative radiation must be potentially indicated for at least one of these lesions.
  • Patients must agree to undergo a research biopsy, if tumor is accessible, at baseline (mandatory) and at the end of cycle 2 of pembrolizumab (optional). .
  • Prior systemic therapy: Patients must be at least 2 weeks from prior chemotherapy, biological agents, immunotherapy or any investigational drug product, with adequate recovery of toxicity. For investigational agents, the minimum time from prior therapy is 5 half-lives if this is longer than 2 weeks in duration.
  • Prior radiation therapy: Patients must be at least 2 weeks from prior radiation therapy
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  • Concurrent administration of other cancer specific therapy during the course of this study is not allowed.
  • Only patients 18 years and older are eligible. There is no upper age limit but the patients must be able to medically tolerate the regimen. Adverse event data are currently unavailable on the use immune checkpoint blockade for participants < 18 years of age, and thus children are excluded from this study.
  • ECOG performance status <=1 (see Appendix A).
  • Ability to understand and the willingness to sign a written informed consent document
  • Female subjects of childbearing potential must have a negative serum pregnancy test at screening.
  • Female and male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in section 5.7.1. Contraception is required prior to study entry and for the duration of study participation and 4 months after completion of pembrolizumab administration.
  • --Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Participants must have normal organ and marrow function as defined below:
  • leukocytes ≥3,000/mcl
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin >= 9 g/dl
  • total bilirubin ≤1.5 × institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
  • AST(SGOT)/ALT(SGPT) For patients with documented liver metastases, ≤ 5 × institutional ULN
  • creatinine ≤1.5 ×within normal institutional ULN OR
  • creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional ULN.
  • International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Activated Partial Thromboplastin Time (aPTT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Laboratory tests required for eligibility must be completed within 14 days prior study entry. Baseline tumor measurements must be documented from tests within 28 days of study entry. Other non-laboratory tests must be performed within 28 days of study entry.

Who cannot join

  • Metastatic disease impinging on the spinal cord or threatening spinal cord compression.
  • Surgical fixation of bone lesion to be irradiated is required and indicated to provide mechanical stability.
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 2 weeks prior to trial therapy initiation, are neurologically stable, and have recovered from the acute effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks before the initiating protocol therapy. Treatment for brain metastases may include surgery, whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician.
  • Participants who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or previous toxicity attributed to pembrolizumab or other PD-1 directed therapy that led to drug discontinuation.
  • Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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  • Clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval >500 ms).
  • Pregnant women are excluded from this study because immunotherapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with immunotherapy, breastfeeding should be discontinued if the mother is treated on this protocol.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances: if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; or if diagnosed and treated for cervical cancer in situ or basal cell or squamous cell carcinoma of the skin.
  • HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for interaction between immunotherapy and these medications.
  • Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non infectious pneumonitis.
  • Active, suspected or prior documented autoimmune disease that has required systemic treatment in the last 2 years with immune modifying agents (e.g. replacement therapy such as thyroxine, insulin or physiologic corticosteroids is not an exclusion criteria).
  • The subject is known to be positive for HepBsAg, or HCV RNA.
  • Lack of availability for follow up assessments.
  • The investigator's belief that the subject is medically unfit to receive pembrolizumab and or unsuitable for any other reason.
  • Has received a live vaccine within 30 days of planned start of study therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Targeting PD-1 Therapy Resistance With Focused High or High and Low Dose Radiation in Squamous Cell Carcinoma of the Head and Neck (SCCHN)

This research study is studying immunotherapy in combination with radiation therapy as a possible treatment for head \& neck cancer that has worsened or spread to another organ or part of your body.

The immunotherapy involved in this study is: MK-3475 (pembrolizumab or KEYTRUDA).

Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational treatment to learn whether the treatment works in treating a specific disease. "Investigational" means that the treatment is being studied.

MK-3475 is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance (particles not typically found in the body such as bacteria or viruses). Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients. MK-3475 is designed to restore the natural ability of the immune system to recognize and target cancer cells.

The FDA recently granted approval to MK-3475 as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). This study is testing whether using radiation in combination with MK-3475 will make this drug work better in participants that might otherwise be unlikely to benefit from this drug because they have not responded to either this same drug given without radiation or another similar drug.

Keywords
Head and Neck Cancer
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    Keytruda is designed to restore the natural ability of the immune system to recognize and target cancer cells

  • RadiationRadiation

    Radiation is used to shrink the cancer

Study groups in NCT03085719
Study groupRoleWhat they receive
High Dose Radiation + PembrolizumabExperimental* High dose radiation will be given in 3 fractions * Pembrolizumab administered intravenously on day one of each cycle.
Receives: Drug: Pembrolizumab; Radiation: Radiation
High Dose + Low Dose Radiation + PembrolizumabExperimental* High Dose radiation will be given in 3 fractions * Low Dose Radiation will be given in 2 fractions * Pembrolizumab administered intravenously on day one of each cycle.
Receives: Drug: Pembrolizumab; Radiation: Radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Surival

    The primary endpoint of this study is progression-free survival (PFS) rate at 3 months. Patients are considered progression-free at 3 months if progression is not observed at the 3-month disease assessment. PFS is defined as the time from registration to disease progression per RECIST or death, whichever occurred first.

    Progressive Disease is defined as at least a 20% increase in the sum of diameters of target lesions, which must also demonstrate an absolute increase of at least 5 mm (with reference to the smallest sum on study). The appearance of one or more new lesions is also considered progressions (RECIST guidelines version 1.1).

    Measured: 1 year

Secondary outcomes (7)

  1. Overall Survival

    Measured: 1 year

  2. Overall Response Rate

    Measured: 1 year

  3. Number of Patients With Treatment Related Adverse Events as Assessed by CTCAE v4.0

    Measured: 1 year

  4. Objective Response by Immune Related Response Criteria (irRC)

    Measured: 1 year

  5. Local Response Determined Using CT Imaging

    Measured: 1 year

  6. Clinical Benefit Rate

    Measured: 1 year

  7. Abscopal Response Determined Using CT Imaging

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2017
  2. Study start30 Jun 2017
  3. Primary completion1 Nov 2022
  4. Study completion31 Oct 2027 (estimated)

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03085719
Sponsor's protocol ID
16-604
Status last verified
May 2026
First submitted
10 Mar 2017
Last updated
15 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • So J, Droznin AD, Tiwari P, Chen YH, Chau NG, Margalit DN, Tishler RB, Hanna GJ, Mak RH, Fitzgerald KJ, Sehgal K, Li S, Gunasti L, Kim E, Minken J, Baginska J, Nau A, Diaz IG, Shim B, Janes JT 3rd, Uppaluri R, Haddad RI, Livak KJ, Schoenfeld JD. Stereotactic Body Radiation Therapy With Pembrolizumab in Programmed Cell Death Protein 1 Inhibitor-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2026 May 1;125(1):64-77. doi: 10.1016/j.ijrobp.2025.12.043. Epub 2026 Jan 9.

    PubMed 41520892

  • Li H, Kwon J, Kim HJ, Kim BH. Immune-modulatory effects of low-dose radiotherapy through macrophage polarization and transcriptional rewiring in triple-negative breast cancer. Biochem Biophys Res Commun. 2025 Oct 30;786:152711. doi: 10.1016/j.bbrc.2025.152711. Epub 2025 Sep 26.

    PubMed 41046657

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Radiation in people with Head and Neck Cancer, run by Dana-Farber Cancer Institute at 1 site 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 26 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 10 Jan 2024). 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 Surival (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03085719, which also lists 2 linked publications.

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 15 Jun 2026.

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