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Clinical Trial 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.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of BAY 1895344 with concurrent head and neck stereotactic body radiation therapy (SBRT) reirradiation and pembrolizumab. II. To determine the recommended phase 2 dose (RP2D) of BAY 1895344 in combination with concurrent head and neck SBRT and pembrolizumab. SECONDARY OBJECTIVE: I. To observe and record anti-tumor activity (overall response rate, progression-free survival, and overall survival) of BAY 1895344, SBRT, and pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC). EXPLORATORY OBJECTIVE: I. To identify predictive biomarkers of response to BAY 1895344, SBRT, and pembrolizumab, including, but not limited to the following: genetic alterations of ATM and other deoxyribonucleic acid (DNA) damage response genes, tumor mutational load, circulating tumor DNA, baseline tumor ATM expression, tumor PD-L1 expression, and change in circulating Ki67+ CD8+ T-cells relative to baseline. OUTLINE: This is a dose-escalation study of BAY 1895344 and stereotactic body radiation therapy (SBRT) given with fixed-dose pembrolizumab. Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Starting on day 7, patients also receive BAY 1895344 orally (PO) twice daily (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 computed tomography (CT) scan and/or positron emission tomography (PET)-CT scan and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 13 weeks for at least 24 months. ;


Study Design


Related Conditions & MeSH terms

  • Carcinoma
  • Carcinoma, Squamous Cell
  • Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • Laryngeal Neoplasms
  • Lip Neoplasms
  • Mouth Neoplasms
  • Oropharyngeal Neoplasms
  • Recurrence
  • 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
  • Salivary Gland Neoplasms
  • Squamous Cell Carcinoma of Head and Neck
  • 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 Oropharyngeal (p16-Negative) Carcinoma 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 Oropharyngeal (p16-Negative) Carcinoma AJCC v8
  • 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

NCT number NCT04576091
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Active, not recruiting
Phase Phase 1
Start date July 6, 2022
Completion date November 27, 2024

See also
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