Oral Cavity Squamous Cell CarcinomaPhase 2NEO COMBAT XLNCT07484139
H&N NEO-COMBAT XL: Neoadjuvant XL-092 (Zanzalintinib) and Pembrolizumab (Keytruda) in Surgically Resectable, HPV Negative Oral Cavity Squamous Cell Carcinoma (OCSCC)
A Phase 2 study testing XL092 and Pembrolizumab in people with Oral Cavity Squamous Cell Carcinoma and Head and Neck Cancer, run by UNC Lineberger Comprehensive Cancer Center at 3 sites in United States.
Trial summary
This is a multicenter, single arm Phase 2B study in subjects with locally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease. The study will assess the combination of neoadjuvant XL092 and pembrolizumab for safety and improvement of pathologic response rates compared to historical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Cavity Squamous Cell Carcinoma, Head and Neck Cancer
- What is being tested?
- XL092 and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2026to May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
- Age ≥ 18 years at the time of consent.
- Tumors must have PD-L1 Combined Positive Score (CPS) ≥ 1.
- ECOG or Karnofsky Performance Status of 0-1
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) within 30 days prior to treatment .
Who cannot join
- Known HPV-positive cancer
- Active infection requiring systemic therapy.
- Prior treatment with XL-092
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
Emory University
Atlanta, Georgia, 30322
Nikki C Schmitt, Nicole.cherie.schmitt@emory.edu
Nikki C Schmitt, MD
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Siddharth Sheth, MD, siddharth.sheth@unchealth.unc.edu
Rose Hall, MSW, 984-974-8440, rose_hall@med.unc.edu
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
This is a multicenter, single arm Phase 2B study in subjects with locally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease. The study will assess the combination of neoadjuvant XL092 and pembrolizumab for safety and improvement of pathologic response rates compared to historical standard of care with perioperative pembrolizumab. The primary objective is to estimate the pathologic response rate defined as either pathological complete response (pCR), which is the absence of residual viable tumor, or major pathologic response (MPR), which is <10% of residual tumor following the completion of neoadjuvant therapy and surgery. The study will be conducted in two stages. Per Simon's Stage 1, 11 patients will be enrolled. Simon Stage 2 will be gated on multiple factors. If ≥2 pathologic response is observed (pCR or MPR), the trial will proceed with cohort expansion and enroll an additional 15 patients for a total of 26 patients.
- Being tested
- XL092, Pembrolizumab
- Keywords
- surgically resectable, neoadjuvant treatment, XL092, pembrolizumab, pathologic response, HPV negative
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XL092Drug
60 mg oral once a day
PembrolizumabDrug
200 mg intravenous for 30 minutes in every 21 days for
| Study group | Role | What they receive |
|---|---|---|
| Locally advanced oral cavity squamous cell carcinoma | Experimental | Locally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease. Receives: Drug: XL092; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of pathologic response
Rate of pathologic response, assessed following surgery, will be defined as either pathological complete response (pCR), which is the absence of residual viable tumor or major pathological response (MPR), which is <10% residual tumor.
Measured: Up to 66 days
Secondary outcomes (5)
Neoadjuvant Adverse Events
Safety will be defined as the rate of treatment emergent adverse events with neoadjuvant XL-092 and pembrolizumab (CTCAE v5.0).
Measured: Up to 66 days
Events Free Survival (EFS)
EFS will be defined as the time from first treatment to an event which may include disease progression, discontinuation of the treatment for any reason, or death from any cause, where disease progression will be determined based on Radiographic response will be measured according to Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). RECIST indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 15 months
Objective response rate (ORR)
ORR following neoadjuvant therapy: an objective response will be classified per the Radiographic response will be measured according to Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1) if a partial or complete response is observed. RECIST indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 15 months
Time to surgery
Time to surgery: defined as the time from completion of neoadjuvant therapy to date of surgery. Individuals who do not receive surgery due to progressive disease, non-TEAE death or individuals who experience surgery delays due to toxicity will not be counted.
Measured: Up to 66 days
Overall survival (OS)
OS is defined as the time from time of first treatment to death due to any cause.
Measured: Up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study startSep 2026 (estimated)
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oral Cavity Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis
- Responsible party
- Sponsor
- Investigators
- Siddharth Sheth, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07484139
- Sponsor's protocol ID
- LCCC2517
- Acronym
- NEO COMBAT XL
- Status last verified
- Aug 2026
- First submitted
- 16 Mar 2026
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- H&N NEO-COMBAT XL: Neoadjuvant XL-092 (Zanzalintinib) and Pembrolizumab (Keytruda) in Surgically Resectable, HPV Negative Oral Cavity Squamous Cell Carcinoma (OCSCC)
- ClinicalTrials.gov ID
- NCT07484139
- Acronym / sponsor ID
- NEO COMBAT XL / LCCC2517
- Keywords
- surgically resectable, neoadjuvant treatment, XL092, pembrolizumab, pathologic response, HPV negative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Exelixis
- Study start
- Sep 2026 (estimated)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 19 Mar 2026 (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 is a multicenter, single arm Phase 2B study in subjects with locally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease. The study will assess the combination of neoadjuvant XL092 and pembrolizumab for safety and improvement of pathologic response rates compared to historical standard of care with perioperative pembrolizumab. The primary objective is to estimate the pathologic response rate defined as either pathological complete response (pCR), which is the absence of residual viable tumor, or major pathologic response (MPR), which is <10% of residual tumor following the completion of neoadjuvant therapy and surgery. The study will be conducted in two stages. Per Simon's Stage 1, 11 patients will be enrolled. Simon Stage 2 will be gated on multiple factors. If ≥2 pathologic response is observed (pCR or MPR), the trial will proceed with cohort expansion and enroll an additional 15 patients for a total of 26 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Locally advanced oral cavity squamous cell carcinoma | Experimental | Drug: XL092, Drug: PembrolizumabLocally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
- Age ≥ 18 years at the time of consent.
- Tumors must have PD-L1 Combined Positive Score (CPS) ≥ 1.
- ECOG or Karnofsky Performance Status of 0-1
Key exclusion criteria (4 listed)
- Known HPV-positive cancer
- Active infection requiring systemic therapy.
- Prior treatment with XL-092
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
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 |
|---|---|---|
| XL09260 mg oral once a day | Drug | Locally advanced oral cavity squamous cell carcinoma |
| Pembrolizumab200 mg intravenous for 30 minutes in every 21 days for | Drug | Locally advanced oral cavity squamous cell carcinoma |
Primary outcome
Rate of pathologic response
Time frame: Up to 66 days
Rate of pathologic response, assessed following surgery, will be defined as either pathological complete response (pCR), which is the absence of residual viable tumor or major pathological response (MPR), which is <10% residual tumor.
5 secondary outcomes
Neoadjuvant Adverse Events
Time frame: Up to 66 days
Events Free Survival (EFS)
Time frame: Up to 15 months
Objective response rate (ORR)
Time frame: Up to 15 months
Time to surgery
Time frame: Up to 66 days
Overall survival (OS)
Time frame: Up to 15 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
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.
Siddharth Sheth, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
3 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 XL092 and Pembrolizumab in people with Oral Cavity Squamous Cell Carcinoma and Head and Neck Cancer, run by UNC Lineberger Comprehensive Cancer Center at 3 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 6 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: opening soon, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rose Hall (919-984-0000, rose_hall@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of pathologic response (time frame: Up to 66 days). 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 31 Aug 2026.