| Eligibility |
Inclusion Criteria:
- 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
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load (e.g., HCV ribonucleic acid [RNA]
[qualitative] is not detected)
- Patients with previously treated brain metastases may participate provided they are
stable (without evidence of progression by imaging using the identical imaging
modality for each assessment, either magnetic resonance imaging [MRI] or computed
tomography [CT] scan, for at least 4 weeks prior to the first dose of trial treatment
and any neurologic symptoms have returned to baseline), have no evidence of new or
enlarging brain metastases, and are not using steroids for at least 7 days prior to
trial treatment
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial (e.g. basal cell carcinoma,
early-stage differentiated thyroid carcinoma, low-risk prostate cancer, ductal
carcinoma in situ of the breast, squamous cell carcinoma of the skin that has
undergone potentially curative therapy, in situ cervical cancer). Patients with 10 or
fewer distant metastases may be eligible for this trial if they meet performance
status inclusion criteria
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association functional classification. To be
eligible for this trial, patients should be class 2B or better
- Enrolling site must perform PD-L1 testing on tumor biopsy per institutional protocol
(local testing or tissue sent to outside laboratory for PD-L1 immunohistochemistry
(IHC) 22C3 pharmDx). Combined positive score (CPS) is recommended for PD-L1 scoring.
Test result does not need to be available at the time of enrollment and treatment
initiation, unless the patient has not received prior platinum-containing
chemotherapy. For patients without a history of platinum-containing chemotherapy,
PD-L1 testing with CPS >= 1 is required to be eligible to receive pembrolizumab
- Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. The effects of BAY 1895344 on the developing human fetus are
unknown. For this reason and because DNA-damage response inhibitors as well as other
therapeutic agents used in this trial are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception prior to
study entry, for the duration of study participation, and for 6 months after
completion of BAY 1895344 therapy or 4 months after completion of pembrolizumab
therapy, whichever is later. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 6 months after completion of BAY 1895344 therapy or 4 months after
completion of pembrolizumab therapy, whichever is later
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the patient
- Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
Exclusion Criteria:
- 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
- Pregnant women are excluded from this study because BAY 1895344 as a DNA-damage
response inhibitor may have the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with BAY 1895344, breastfeeding should be
discontinued if the mother is treated with BAY 1895344 and for 4 months after the end
of BAY 1895344 treatment. These potential risks may also apply to other agents used in
this study
- Has a known history of active tuberculosis (TB)
- Has received a live vaccine within 30 days of planned treatment start. Seasonal flu
vaccines that do not contain live virus are permitted. Similarly, coronavirus disease
2019 (COVID-19) vaccines are permitted
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