Head and Neck Squamous Cell CarcinomaEarly Phase 1NCT06308913
Pembrolizumab, INCB081776, and Radiation Therapy for Head and Neck Squamous Cell Carcinoma
A Early Phase 1 study testing INCB081776, Pembrolizumab and Palliative RT in people with Head and Neck Squamous Cell Carcinoma, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
This study is evaluating INCB081776 when given in combination with the checkpoint inhibitor pembrolizumab and palliative radiation therapy in patients with metastatic or recurrent metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- INCB081776, Pembrolizumab and Palliative RT
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Sep 2024to 16 Sep 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- Participants must have histologic or cytologic evidence of head and neck squamous cell carcinoma (HNSCC) that is metastatic or recurrent and therefore considered incurable. Cutaneous skin squamous cell carcinomas located in the head and neck region are eligible after discussion with the Sponsor-Investigator.
- Measurable disease that are considered non-amenable to surgery or other curative treatments or procedures, with at least 1 target lesion available for evaluation.
- The preference is for measurable disease to be selected from a site that has not received any prior radiation or locoregional therapy. However, if a tumor lesion is situated in a previously irradiated area, or in an area subjected to other prior locoregional therapy, the lesion should demonstrate disease progression after the prior treatment.
- Prior cancer treatment must be completed at least 14 days prior to enrollment (for chemotherapy, targeted small molecular therapy, or radiation therapy. Prior treatment with a monoclonal antibody must be completed at least 28 days prior to enrollment. Participants must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.
- Participants must have two "index" tumors that meet the following criteria:
- Index tumor A (lesion to receive palliative radiation therapy):
Show all 20Show fewer
- is deemed by the treating radiation oncologist to potentially benefit from palliative radiation
- is at least 1 cm in longest dimension for lesions not located in the bone, if radiating bone, presence of a bone lesion is sufficient.
- Index tumor B (lesion to undergo biopsy):
- Is deemed by the treating physician to be amenable to biopsy
- Is at least 1 cm in longest dimension.
- Participants must be willing to provide at least 2 research biopsies (up to 3 research biopsies) during the conduct of the study.
- Note: If a subject is scheduled to have a baseline or on-study tumor biopsy, and the investigator believes that the tumor tissue cannot be obtained safely, then the biopsy may be omitted with approval by the Sponsor-Investigator. The participant may be replaced in order to enroll sufficient number of subjects for biomarker evaluation.
- Note: Care should be taken to biopsy the same lesions for research samples. The preference is for the same lesion to be biopsied at all time points. If a lesion is no longer amenable for a research biopsy (for examples: due to a decrease in size, becomes inaccessible, is not safe/feasible for a biopsy), then an alternative lesion may be utilized with approval by the Sponsor-Investigator. Index tumor B (lesion to undergo biopsy) must not have received palliative radiation therapy during the study.
- Participants must be willing to provide at least 2 collections of fresh research biopsies (up to 3 fresh research biopsies) during the conduct of this study.
- Research biopsy #1 (baseline, mandatory). Archival tissue obtained since completion of last therapy may be used.
- Research biopsy #2 (cycle 1 days 9-14, after treatment with INCB081776 but prior to pembrolizumab, mandatory)
- Research biopsy #3 (cycle 1 day 37-56, after treatment with INCB081776, pembrolizumab and palliative RT). For participants who had baseline archival tissue collected (no baseline research biopsy was obtained), this fresh core biopsy is mandatory. For participants who underwent a fresh core research biopsy at baseline, this biopsy is optional.
- Note: If a participant is scheduled to have an on-study tumor biopsy, and the investigator believes that the tumor tissue cannot be obtained safely, then the biopsy may be omitted after discussion with the Sponsor-Investigator. The participant may be replaced in order to enroll sufficient number of subjects for biomarker evaluation.
- Note: Care should be taken to biopsy the same lesion for the on-treatment samples
Who cannot join
- Subjects with significant intercurrent illnesses per physician discretion.
- Subjects with a diagnosed auto-immune disease requiring systemic treatment with immunosuppressants.
- Subjects with known genetic conditions causing pre-disposition to RT toxicity (i.e: Li-Fraumeni, ATM deficiency, active scleroderma, etc.).
- Subjects with known retinal or ophthalmologic disorders or conditions. Subjects with macular degeneration, proliferative diabetic retinopathy or diabetic retinopathy with macular edema, retinal vein occlusions, uveitis, central serous retinopathy, leukemic retinopathy, inherited retinal degenerations, known family history of inherited retinal degenerations, and subjects at risk for angle closure glaucoma from pupillary dilation are ineligible. Subjects with other clinically significant abnormalities identified during ophthalmic screening examinations that may confound ocular monitoring are ineligible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study of INCB081776 Together With Palliative Radiation and Anti-PD-1 Checkpoint Blockade With Pembrolizumab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
This study is evaluating INCB081776 when given in combination with the checkpoint inhibitor pembrolizumab and palliative radiation therapy in patients with metastatic or recurrent metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). 12 participants will be enrolled and can expect to be on study for up to 12 months.
Read the detailed description
Primary Objective
- To evaluate the safety and tolerability of INCB081776 in combination with pembrolizumab and standard palliative radiation therapy in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck.
Secondary Objectives
- To determine the preliminary efficacy of INCB081776 in combination with pembrolizumab plus palliative radiation therapy in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck. The irradiated lesion (lesion A) will not be included in the analysis.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- INCB081776, Pembrolizumab, Palliative RT
- Keywords
- metastatic
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INCB081776Drug
INCB081776 will be given orally on a daily basis. The highest safe/tolerable dose and schedule will be established by the ongoing phase 1 clinical trial of INCB081776 plus INCBMGA00012 (NCT03522142), which is 120 mg daily.
PembrolizumabDrug
Immune checkpoint blockade with anti-PD-1 (Pembrolizumab) will be given as 200 mg IV on cycle 1 day 15 and cycle 1 day 36. Starting from cycle 2, pembrolizumab will be given on day 1 on each subsequent cycle.
Palliative RTRadiation
Palliative RT will be given as either 24 Gy in 3 fractions (8 Gy per fraction) or 20 Gy in 5 fractions (4 Gy per fraction). The palliative radiation therapy dose will be determined based on the clinical judgment of the treating radiation oncology physician. Palliative RT must be completed between cycle 1 day 29 to cycle 1 day 33. After completion of palliative radiation therapy, patients will continue with additional cycles of INCB081776 and pembrolizumab until disease progression, intolerance to the combination regimen, or patient withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| INCB081776/Pembrolizumab and RT for HNSCC | Experimental | Cycle 1 of this clinical trial is 56 days in duration to allow for the systematic addition of each agent to the combination regimen. For cycle 2 and all subsequent cycles, the treatment cycle will be 21 days in length. Receives: Drug: INCB081776; Drug: Pembrolizumab; Radiation: Palliative RT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AEs)
Frequency of AEs through physical examinations, by evaluating changes in vital signs, through clinical laboratory blood sample evaluations.
Measured: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)
Duration of Adverse Events
Duration of AEs through physical examinations, by evaluating changes in vital signs, through clinical laboratory blood sample evaluations.
Measured: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)
Severity of Adverse Events
Severity of AEs through physical examinations, by evaluating changes in vital signs, through clinical laboratory blood sample evaluations. Severity will be reported by Grade between 1 (mild) and 5 (death).
Measured: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)
Secondary outcomes (3)
Overall response rate (ORR)
Defined as the percentage of participants having CR or PR per RECIST 1.1. The irradiated lesion (lesion A) will not be included in the analysis.
Measured: up to 12 months
Disease control rate (DCR)
Defined as the percentage of participants having complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.
Measured: up to 12 months
Duration of response (DoR)
Defined as the time from earliest date of response until the earliest date of disease progression or death per RECIST 1.1 due to any cause, if occurring sooner than progression.
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2024
- Study start18 Sep 2024
- Primary completion16 Sep 2026
- Study completion16 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR), National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Justine Bruce, MD, Principal investigator, University of Wisconsin, MadisonDeric Wheeler, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06308913
- Sponsor's protocol ID
- 2023-1722
- Other IDs
- UW23121, A534260, Protocol Version 6/3/2025, P50CA278595
- Status last verified
- Oct 2026
- First submitted
- 5 Mar 2024
- Last updated
- 4 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of INCB081776 Together With Palliative Radiation and Anti-PD-1 Checkpoint Blockade With Pembrolizumab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT06308913
- Acronym / sponsor ID
- 2023-1722
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Keywords
- metastatic
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR), National Cancer Institute (NCI)
- Study start
- 18 Sep 2024 (actual)
- Primary completion
- 16 Sep 2026 (actual)
- Study completion
- 16 Sep 2026 (actual)
- First posted
- 13 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is evaluating INCB081776 when given in combination with the checkpoint inhibitor pembrolizumab and palliative radiation therapy in patients with metastatic or recurrent metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). 12 participants will be enrolled and can expect to be on study for up to 12 months.
Detailed description
Primary Objective
- To evaluate the safety and tolerability of INCB081776 in combination with pembrolizumab and standard palliative radiation therapy in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck.
Secondary Objectives
- To determine the preliminary efficacy of INCB081776 in combination with pembrolizumab plus palliative radiation therapy in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck. The irradiated lesion (lesion A) will not be included in the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| INCB081776/Pembrolizumab and RT for HNSCC | Experimental | Drug: INCB081776, Drug: Pembrolizumab, Radiation: Palliative RTCycle 1 of this clinical trial is 56 days in duration to allow for the systematic addition of each agent to the combination regimen. For cycle 2 and all subsequent cycles, the treatment cycle will be 21 days in length. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Participants must have histologic or cytologic evidence of head and neck squamous cell carcinoma (HNSCC) that is metastatic or recurrent and therefore considered incurable. Cutaneous skin squamous cell carcinomas located in the head and neck region are eligible after discussion with the Sponsor-Investigator.
- Measurable disease that are considered non-amenable to surgery or other curative treatments or procedures, with at least 1 target lesion available for evaluation.
- Prior cancer treatment must be completed at least 14 days prior to enrollment (for chemotherapy, targeted small molecular therapy, or radiation therapy. Prior treatment with a monoclonal antibody must be completed at least 28 days prior to enrollment. Participants must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.
- Participants must have two "index" tumors that meet the following criteria:
- Participants must be willing to provide at least 2 collections of fresh research biopsies (up to 3 fresh research biopsies) during the conduct of this study.
Key exclusion criteria (4 listed)
- Subjects with significant intercurrent illnesses per physician discretion.
- Subjects with a diagnosed auto-immune disease requiring systemic treatment with immunosuppressants.
- Subjects with known genetic conditions causing pre-disposition to RT toxicity (i.e: Li-Fraumeni, ATM deficiency, active scleroderma, etc.).
- Subjects with known retinal or ophthalmologic disorders or conditions. Subjects with macular degeneration, proliferative diabetic retinopathy or diabetic retinopathy with macular edema, retinal vein occlusions, uveitis, central serous retinopathy, leukemic retinopathy, inherited retinal degenerations, known family history of inherited retinal degenerations, and subjects at risk for angle closure glaucoma from pupillary dilation are ineligible. Subjects with other clinically significant abnormalities identified during ophthalmic screening examinations that may confound ocular monitoring are ineligible.
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 |
|---|---|---|
| INCB081776INCB081776 will be given orally on a daily basis. The highest safe/tolerable dose and schedule will be established by the ongoing phase 1 clinical trial of INCB081776 plus INCBMGA00012 (NCT03522142), which is 120 mg daily. | Drug | INCB081776/Pembrolizumab and RT for HNSCC |
| PembrolizumabImmune checkpoint blockade with anti-PD-1 (Pembrolizumab) will be given as 200 mg IV on cycle 1 day 15 and cycle 1 day 36. Starting from cycle 2, pembrolizumab will be given on day 1 on each subsequent cycle. | Drug | INCB081776/Pembrolizumab and RT for HNSCC |
| Palliative RTPalliative RT will be given as either 24 Gy in 3 fractions (8 Gy per fraction) or 20 Gy in 5 fractions (4 Gy per fraction). The palliative radiation therapy dose will be determined based on the clinical judgment of the treating radiation oncology physician. Palliative RT must be completed between cycle 1 day 29 to cycle 1 day 33. After completion of palliative radiation therapy, patients will continue with additional cycles of INCB081776 and pembrolizumab until disease progression, intolerance to the combination regimen, or patient withdrawal. | Radiation | INCB081776/Pembrolizumab and RT for HNSCC |
Primary outcome
Incidence of Adverse Events (AEs)
Time frame: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)
Frequency of AEs through physical examinations, by evaluating changes in vital signs, through clinical laboratory blood sample evaluations.
Duration of Adverse Events
Time frame: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)
Duration of AEs through physical examinations, by evaluating changes in vital signs, through clinical laboratory blood sample evaluations.
Severity of Adverse Events
Time frame: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)
Severity of AEs through physical examinations, by evaluating changes in vital signs, through clinical laboratory blood sample evaluations. Severity will be reported by Grade between 1 (mild) and 5 (death).
3 secondary outcomes
Overall response rate (ORR)
Time frame: up to 12 months
Disease control rate (DCR)
Time frame: up to 12 months
Duration of response (DoR)
Time frame: up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: No
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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.
Justine Bruce, MD principal investigator
University of Wisconsin, Madison
Deric Wheeler, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing INCB081776, Pembrolizumab and Palliative RT in people with Head and Neck Squamous Cell Carcinoma, run by University of Wisconsin, Madison 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 20 inclusion and 4 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 4 Nov 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of Adverse Events (AEs) (time frame: Participants will be followed for 30 days (+/- 7 days) after the last dose of treatment (up to 12 months on study)). The study lists 3 primary outcomes in all. 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 4 Nov 2026.