Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer
Phase I Trial of BAY 1895344 ATR Inhibitor Combined With Stereotactic Body Radiation Therapy and Pembrolizumab for Recurrent Head and Neck Squamous Cell Carcinoma
4 other identifiers
interventional
7
1 country
11
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2022
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2020
CompletedFirst Posted
Study publicly available on registry
October 6, 2020
CompletedStudy Start
First participant enrolled
July 6, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 22, 2025
CompletedResults Posted
Study results publicly available
July 29, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
January 14, 2027
ExpectedAugust 21, 2026
July 1, 2026
3 years
October 3, 2020
November 25, 2025
July 30, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Maximum-tolerated Dose (MTD) (Escalation)
Dose of elimusertib (BAY 1895344) and concurrent stereotactic (8 Gy x 3 RT) body radiation therapy. Two 3-week cycles of therapy.
Up to 6 weeks
Incidence of Dose Limiting Toxicities (DLT)
Number of patients who experienced Dose Limiting Toxicities. DLTs are defined as occurrence of any of the following events, if judged by the Investigator to be possibly, probably or definitely related to study drug administration 1. Any Grade 4 or greater adverse event per the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5.0) observed within 90 days of the last dose of radiation therapy. 2. Grade 3 nonhematologic toxicity (not laboratory) lasting \>5 days despite optimal supportive care. 3. Any Grade 3 nonhematologic laboratory value if: • Medical intervention is required to treat the patient, or • The abnormality leads to hospitalization, or • The abnormality persists for \>1 week. 4. Febrile neutropenia. 5. Thrombocytopenia \<25000/mm3 if associated with bleeding requiring intervention. 6. Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity.
Within 90 days of treatment initiation
Dose of BAY 1895344
Dose of elimusertib (BAY 1895344) and concurrent stereotactic (8 Gy x 3 RT) body radiation therapy. Two 3-week cycles of therapy.
Up to 6 weeks
Incidence of Late Adverse Events
Number of patients that experienced Adverse Events and/or Serious Adverse Events assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 5, at least possibly related to treatment.
After 90 days post discontinuation of treatment, up to 1 year
Secondary Outcomes (13)
Incidence of Adverse Events
Up to 12 months
Locoregional Control
Up to 2 years
Overall Response Rate
Up to 2 years
Progression-free Survival
Up to 2 years
1-year Progression-free Survival
At 1 year
- +8 more secondary outcomes
Other Outcomes (1)
Potential Predictive Biomarkers of Response
Up to 2 years
Study Arms (1)
Treatment (pembrolizumab, BAY 1895344, SBRT)
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Starting on day 7, patients also receive BAY 1895344 PO BID on days 7-9 and 14-16 during cycle 1, and before and after each SBRT treatment during cycle 2 for a total of 9 doses. Beginning cycle 2, patients undergo SBRT starting between days 2 and 8 for 3 fractions with 2-3 days between fractions. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or PET-CT scan and collection of blood samples throughout the trial.
Interventions
Undergo blood sample collection
Undergo CT and/or PET-CT scan
Undergo SBRT
Given PO
Given IV
Undergo PET-CT scan
Ancillary studies
Eligibility Criteria
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
- +17 more criteria
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
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Yvonne Mowery, MD
- Organization
- UPMC Hillman Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Yvonne M Mowery
University of Pittsburgh Cancer Institute LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 3, 2020
First Posted
October 6, 2020
Study Start
July 6, 2022
Primary Completion
July 22, 2025
Study Completion (Estimated)
January 14, 2027
Last Updated
August 21, 2026
Results First Posted
July 29, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.