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NCT03468218

Pembrolizumab & Cabozantinib in Patients With Head and Neck Squamous Cell Cancer

Active, enrolled Phase 2 Results posted Last updated 23 January 2026
What this trial tests

Phase 2 trial testing Cabozantinib in Metastatic Head and Neck Carcinoma in 36 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
18 September 2018
Primary endpoint
2 May 2022
29 October 2026

Quick facts

Lead sponsorEmory University
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment36
Start date18 September 2018
Primary completion2 May 2022
Estimated completion29 October 2026
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Emory University

Who can join

18 and older, any sex, with Metastatic Head and Neck Carcinoma or Paranasal Sinus Squamous Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Primary · Up to 2 years after treatment start

Will assess the proportion of subjects with partial response or complete response as defined by Response Evaluation Criteria in Solid Tumors version 1.1 response criteria. ORR will be calculated with 95% confidence interval by binomial distribution. The ability of biomarkers to predict ORR will be estimated by chi-square test and/or logistic regression model.

GroupValue95% CI
Treatment (Pembrolizumab, Cabozantinib)52
Progression Free Survival (PFS) Secondary · Duration from date of treatment start to the date of objectively documented progression or death due to any cause, whichever status is recorded first, assessed up to 2 years

The median PFS will be estimated by Kaplan-Meier method along with 95% confidence interval. The biomarker association with PFS will be assessed by the Kaplan-Meier method, log-rank test, and Cox model.

GroupValue95% CI
Treatment (Pembrolizumab, Cabozantinib)5431.5 – 72

Adverse events — posted to ClinicalTrials.gov

Time frame: 2 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Pembrolizumab, Cabozantinib)
Serious: 18/36 (50%)
Deaths: 7/36

Serious adverse events (19 terms)

ReactionSystemTreatment (Pembrolizumab, …
DeathGeneral disorders
Hospitalization-hyponatremiaInvestigations
Hospiltaization- acute respiratory failureRespiratory, thoracic and mediastinal disorders
Hospitalization- AspirationGastrointestinal disorders
Hospitalization-TransanitisGastrointestinal disorders
Hospitalization- Low blood pressureVascular disorders
Hospitalization-drug induced hepatitisGastrointestinal disorders
Hospitalization- Atrial FibrillationCardiac disorders
Hospitalization-hypotensionVascular disorders
Hospitalization- Ulcer in right oropharynxGastrointestinal disorders
Hospitalization- HypercalcemiaInvestigations
Hospitalizaiton- PancreatitisGastrointestinal disorders
Hospitalization- lower lung consolidation/ NVRespiratory, thoracic and mediastinal disorders
Hospitalzation- Leukocytosis, sepsis bowel obstructionInfections and infestations
Hospitalizaiton- AnemiaBlood and lymphatic system disorders
Hospitalization- Back PainMusculoskeletal and connective tissue disorders
Hospitalization- TachycardiaCardiac disorders
Hospitalization- DysphagiaGastrointestinal disorders
Hospitalization- Port infectionInfections and infestations
Other adverse events (70 terms — click to expand)

ReactionSystemTreatment (Pembrolizumab, …
FatigueGeneral disorders
DiarrheaGastrointestinal disorders
HypothyroidismEndocrine disorders
HypertensionVascular disorders
ConstipationGastrointestinal disorders
Dry MouthGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
HeadacheNervous system disorders
HyponatremiaMetabolism and nutrition disorders
DysphagiaGastrointestinal disorders
Oral MucositisGastrointestinal disorders
PainGeneral disorders
hypomagnesemiaMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
Sore ThroatRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
Palmer-Plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
HypophosphatemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Oral PainGastrointestinal disorders
Abdominal painGastrointestinal disorders
Maculopapular rashSkin and subcutaneous tissue disorders
Decreased white blood countBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders
Increased ASTMetabolism and nutrition disorders
HypotensionVascular disorders
CoughRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
Respiratory, thoracic and mediastinal disorders-Other, specifyRespiratory, thoracic and mediastinal disorders
Increased alanine aminotransferaseMetabolism and nutrition disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Decreased Platelet CountBlood and lymphatic system disorders
VomitingGastrointestinal disorders
DizzinessNervous system disorders
Investigations- otherInvestigations
Increased gamma-glutamyl transferaseHepatobiliary disorders
Hepatobiliary disorders-Other, specifyHepatobiliary disorders
Increased LipaseInvestigations
DehydrationMetabolism and nutrition disorders
General disorders and administration site conditions- Other, specifyGeneral disorders

Most-reported serious reactions: Death, Hospitalization-hyponatremia, Hospiltaization- acute respiratory failure, Hospitalization- Aspiration, Hospitalization-Transanitis, Hospitalization- Low blood pressure, Hospitalization-drug induced hepatitis, Hospitalization- Atrial Fibrillation.

Data from ClinicalTrials.gov NCT03468218 adverse events section.

Sponsor's own description

This phase II trial studies how well pembrolizumab and cabozantinib in treating patients with head and neck squamous cell cancer that has come back or spread to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the pathways needed for cell growth. Giving pembrolizumab and cabozantinib may improve the chances of tumor response in patients with head and neck squamous cell cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Endothelial cells in tumor microenvironment: insights and perspectives.
    Leone P, Malerba E, Susca N, Favoino E, et al · · 2024 · cited 90× · PMID 38426109 · DOI 10.3389/fimmu.2024.1367875
  2. Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.
    Wei J, Li W, Zhang P, Guo F, et al · · 2024 · cited 82× · PMID 39725966 · DOI 10.1186/s12943-024-02179-5
  3. Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy.
    Horton JD, Knochelmann HM, Day TA, Paulos CM, et al · · 2019 · cited 65× · PMID 30961829 · DOI 10.1016/j.trecan.2019.02.007
  4. Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial.
    Saba NF, Steuer CE, Ekpenyong A, McCook-Veal A, et al · · 2023 · cited 61× · PMID 37012550 · DOI 10.1038/s41591-023-02275-x
  5. BDNF and its signaling in cancer.
    Malekan M, Nezamabadi SS, Samami E, Mohebalizadeh M, et al · · 2023 · cited 48× · PMID 36173463 · DOI 10.1007/s00432-022-04365-8
  6. Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.
    Farlow JL, Brenner JC, Lei YL, Chinn SB. · · 2021 · cited 34× · PMID 34218062 · DOI 10.1016/j.oraloncology.2021.105420
  7. Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer.
    Lang L, Wang F, Ding Z, Zhao X, et al · · 2021 · cited 33× · PMID 34906193 · DOI 10.1186/s13046-021-02207-y
  8. Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion.
    Xia Y, Huang C, Zhong M, Zhong H, et al · · 2025 · cited 32× · PMID 39856684 · DOI 10.1186/s12964-025-02033-1

Verify or expand the search:

Other trials of Cabozantinib

Trials testing the same drug.

Other recruiting trials for Metastatic Head and Neck Carcinoma

Currently open trials in the same condition.

Other Emory University trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03468218.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing