Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer

Running, not enrolling · Phase 1

Conditions studied: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Recurrent Cutaneous Squamous Cell Carcinoma of the Head and Neck, 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, Recurrent Paranasal Sinus Squamous Cell Carcinoma, Recurrent Salivary Gland Carcinoma, Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Major Salivary Gland Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage III Sinonasal Cancer AJCC v8, Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IV Sinonasal Cancer AJCC v8, Unresectable Cutaneous Squamous Cell Carcinoma of the Head and Neck, Unresectable Head and Neck Squamous Cell Carcinoma, Unresectable Hypopharyngeal Squamous Cell Carcinoma, Unresectable Laryngeal Squamous Cell Carcinoma, Unresectable Oral Cavity Squamous Cell Carcinoma, Unresectable Oropharyngeal Squamous Cell Carcinoma, Unresectable Paranasal Sinus Squamous Cell Carcinoma, Unresectable Salivary Gland Squamous Cell Carcinoma

In brief

This phase I trial evaluates the best dose, possible benefits and/or side effects of combination therapy with elimusertib (BAY 1895344), stereotactic body radiation, and pembrolizumab in treating patients with head and neck squamous cell cancer that has come back (recurrent) and cannot be removed by surgery (unresectable). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving BAY 1895344, stereotactic body radiation therapy in combination with pembrolizumab may shrink or stabilize head and neck squamous cell cancer for longer than treatment with radiation and immunotherapy without BAY 1895344.

Key facts

Study ID

NCT04576091

Run by

National Cancer Institute (NCI)

People needed

7

Starts

2022-07-06

Expected to finish

2027-01-14

Last updated by the study team

2026-07-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically confirmed recurrent or metachronous (second primary), unresectable head and neck squamous cell carcinoma, including oral cavity, oropharynx, larynx, hypopharynx, cutaneous, salivary gland, paranasal sinus, or cervical lymphadenopathy (head and neck cancer of unknown primary). Core needle biopsy (preferably at least three 18-gauge cores) or incisional biopsy is preferred over fine needle aspiration (FNA) for diagnosis of recurrent disease or new primary head and neck squamous cell carcinoma to provide sufficient tumor tissue for correlative studies. Unresectable refers both to patients who have declined surgery and patients deemed unresectable by otolaryngology. This includes patients for whom curative resection is medically contraindicated and/or would be associated with excessive surgical risk (as deemed by the consulting otolaryngologist) or undue surgical morbidity (e.g., total glossectomy, laryngectomy, and/or major resection requiring free flap reconstruction)
• Patients must have either recurrent disease or a new primary squamous cell carcinoma of the head and neck within a previously irradiated area (radiotherapy to dose >= 40 Gy, i.e., in-field recurrence)
• Patients must have completed prior radiotherapy >= 6 months prior to enrollment
• Patients must meet at least one of the following criteria: 1) received prior platinum-containing chemotherapy; and/or 2) tumor expresses PD-L1 (Combined Positive Score [CPS] >= 1)
• Patients who have received anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy must have had disease progression while on this therapy. Patients who have not received prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy are also eligible
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of BAY 1895344 with pembrolizumab in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%) and a life expectancy of >= 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL or 5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (If total bilirubin > 1.5 x ULN, direct bilirubin must be < ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (=< 5 x ULN for patients with liver metastases)
• Creatinine OR measured or calculated creatinine clearance (CrCl) < 1.5 x institutional ULN OR glomerular filtration rate (GFR) > 60 mL/min/1.73 m\^2
• CrCl should be calculated per institutional standard
• Albumin > 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Patients must have measurable disease (at least one measurable lesion) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline imaging must include neck CT (preferably contrast-enhanced) and chest CT or skullbase to midthigh PET/CT (preferably with contrast-enhanced neck CT if diagnostic contrast-enhanced neck CT not available). Patients who have undergone surgery aside from biopsy may be included if gross disease is present within the surgical resection bed or at another site
• Patients must have no contraindications to pembrolizumab, including no history of organ allograft transplantation or active autoimmune disease (active defined as having autoimmune disease-related symptoms and detectable autoantibodies) that has required systemic treatment in the past 2 years (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Human immunodeficiency virus (HIV)-infected patients may participate IF they meet the following eligibility requirements:
• They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
• They must have a CD4 count of greater than 250 cells/mcL
• They must not be receiving prophylactic therapy for an opportunistic infection
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (e.g., not hepatitis B surface antigen [HBsAg] reactive), if indicated

You may not qualify if…

• Patients who are unable to take oral medications
• Patients with nasopharyngeal carcinoma, paranasal sinus cancers with histology other than squamous cell carcinoma, or salivary gland cancers with histology other than squamous cell carcinoma
• Patients who have had more than one prior course of head and neck radiotherapy
• Patients who have disease surrounding >= 180 degrees of the carotid artery
• Patients with gross tumor involvement of the mandible
• Patients with widely metastatic disease.
• Note: Patients with oligometastatic disease (defined as ten or fewer distant metastases) may qualify for the study
• Patients who have had chemotherapy, targeted small-molecule therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Note: Patients with =< grade 2 neuropathy or =< grade 2 alopecia are an exception to this criterion and may qualify for the study
• Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Patients who are currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to initiating the study drug BAY 1895344
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
• Has had a prior monoclonal antibody other than anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier.
• Note: Patients who received anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy within 4 weeks prior to study initiation are eligible if they have exhibited disease expression while on this therapy
• Has new or progressive brain metastases, or leptomeningeal disease
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, ductal carcinoma in situ of the breast, early-stage differentiated thyroid cancer, or low-risk prostate cancer. Note: As discussed above, patients with limited metastatic disease (10 or fewer distant metastases) may qualify for the study
• Patients with carcinomatous meningitis should be excluded
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 1893544 or pembrolizumab
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Patients whose disease has improved or remained stable (no evidence of disease progression) while receiving therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent are ineligible
• Patients receiving any medications that are substrates of CYP3A4 with a narrow therapeutic window, or strong inhibitors/inducers of CYP3A4 are ineligible, if they cannot be transferred to alternative medication. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with psychiatric illness/social situations that would limit compliance with study requirements

Where it is running

• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• Northwestern University — Chicago, Illinois, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• Montefiore Medical Center-Einstein Campus — The Bronx, New York, United States
• Montefiore Medical Center - Moses Campus — The Bronx, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• University of Pittsburgh Cancer Institute (UPCI) — Pittsburgh, Pennsylvania, United States
• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States
• Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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