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

NCT03468218 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB00100269NCI-2017-02419Winship4234-17P30CA138292
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Head and Neck Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Paranasal Sinus Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Unresectable Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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.

  Up to 2 years after treatment start

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  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

Study Arms (1)

Treatment (pembrolizumab, cabozantinib)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib; Biological: Pembrolizumab

Interventions

Cabozantinib DRUG

Given PO

Also known as: Cabometyx, Cometriq

Treatment (pembrolizumab, cabozantinib)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, cabozantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, paranasal sinuses, hypopharynx, nasopharynx, or larynx; squamous cell carcinoma of unknown primary in cervical lymph node can be included only if human papillomavirus (HPV) status is positive
• Patients must have refractory, recurrent or metastatic disease, which is deemed to be inoperable
• In case patients received prior systemic therapy within the definitive or metastatic setting, disease progression must be documented following prior therapy; this can be in the recurrent or metastatic setting or in the concurrent setting
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the investigator
• A maximum of one prior radiotherapy regimen, curative or palliative, to the head and neck is allowed; if the radiation is combined with chemotherapy, a minimum of 4 months must elapse between the end of radiotherapy and registration; if the radiation is given alone, a minimum of 8 weeks must elapse between the end of radiotherapy and registration; a minimum of 3 weeks must elapse between prior radiation to other areas and registration; treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
• The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT scan as appropriate, within 28 days before the first dose of cabozantinib
• Life expectancy of greater than 3 months
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Within 7 days before the first dose of cabozantinib: The absolute neutrophil count (ANC) ≥ 1000/mm³ without colony stimulating factor support
• Within 7 days before the first dose of cabozantinib: Platelets ≥ 100,000/mm³
• Within 7 days before the first dose of cabozantinib: Hemoglobin ≥ 9 g/dL
• Within 7 days before the first dose of cabozantinib: Bilirubin ≤ 1.5 x the upper limit of normal (ULN); for subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
• Within 7 days before the first dose of cabozantinib: Serum albumin ≥ 2.8 g/dl
• Within 7 days before the first dose of cabozantinib: Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min; for creatinine clearance estimation, the Cockcroft and Gault equation should be used

You may not qualify if:

• Patients who have HPV negative squamous cell carcinoma of unknown primary in cervical lymph node
• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 4 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
• Prior treatment with cabozantinib or pembrolizumab
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment; systemic treatment with radionuclides within 6 weeks before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
• The subject has received any other type of investigational agent within 28 days or 5 half-lives, whichever is shorter, before the first dose of study treatment
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment; eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
• The subject has prothrombin time (PT)/institutional normalized ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants (eg, warfarin, direct thrombin and factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel)
• Note: Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (\< 1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation with therapeutic doses of LMWH is allowed in subjects who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• The subject has experienced any of the following:
• Clinically-significant GI bleeding within 6 months before the first dose of study treatment
• Hemoptysis of ≥ 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment
• Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• The subject has radiographic evidence of cavitating pulmonary lesion(s)

Sponsors & Collaborators

• Emory University: lead
• Exelixis: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Related Publications (1)

• Saba NF, Steuer CE, Ekpenyong A, McCook-Veal A, Magliocca K, Patel M, Schmitt NC, Stokes W, Bates JE, Rudra S, Remick J, McDonald M, Abousaud M, Tan AC, Fadlullah MZH, Chaudhary R, Muzaffar J, Kirtane K, Liu Y, Chen GZ, Shin DM, Teng Y, Chung CH. Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial. Nat Med. 2023 Apr;29(4):880-887. doi: 10.1038/s41591-023-02275-x. Epub 2023 Apr 3.

  PMID: 37012550 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

cabozantinib; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Dr. Nabil Saba
• Organization: Emory University

nfsaba@emory.edu

404-778-1900

Study Officials

• Nabil F. Saba, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 10, 2018
• First Posted: March 16, 2018
• Study Start: September 18, 2018
• Primary Completion: May 2, 2022
• Study Completion (Estimated): October 29, 2026
• Last Updated: January 23, 2026
• Results First Posted: December 27, 2024

Record last verified: 2026-01

Locations

US (2)