Head and Neck Cancer, Squamous Cell Carcinoma of Head and Neck, Oral Cavity Squamous Cell Carcinoma, Oral Cavity Cancer, Oropharynx Cancer, Oropharynx Squamous Cell Carcinoma, Larynx Cancer, Pharynx Cancer, Hypopharynx Cancer, Hypopharynx Squamous Cell Carcinoma
Conditions
Brief summary
The purpose of this study is to test the safety and tolerability of chemotherapy and radiation in combination with the investigational study drugs zimberelimab (AB122) and etrumadenant (AB928) in subjects with a locally advances head or neck cancer. The study will also ask how the study drugs change the following: * The microbiome that lives in the mouth and on the skin * Immune cells as they respond to a skin wound * Scarring (fibrosis) caused by radiation After completing a screening phase, subjects will be assigned to one of three cohorts: * Cohort 1: Subjects who will receive cisplatin, radiation and zimberelimab followed by zimberelimab only. * Cohort 2: Subjects who will receive cisplatin, radiation, zimberelimab and etrumadenant followed by zimberelimab and etrumadent. * Cohort 3: Subjects who will receive cisplatin and radiation followed by an observation period. All three cohorts will be followed for a 24 months following the conclusion of the chemoradiation.
Interventions
DRUGZimberelimab
Zimberelimab will be administered at a dose of 360 mg IV on Day 1 of each 21-day cycle for up to 11 cycles.
DRUGEtrumadenant
Etrumadenant will be administered at a dose of 150 mg by mouth once daily on days 1-21 of each 21-day cycle for up to 11 cycles.
DRUGCisplatin
Concurrent weekly cisplatin and radiation will be administered as part of the subject's standard of care. Cisplatin and radiation will be initiated on the same day and continue for up to 7.5 weeks.
RADIATIONRadiation
Concurrent weekly cisplatin and radiation will be administered as part of the subject's standard of care. Cisplatin and radiation will be initiated on the same day and continue for up to 7.5 weeks.
Sponsors
Arcus Biosciences, Inc.
Jennifer Choe
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the criteria below apply. 1. Age ≥ 18 years of age. 2. Ability to understand and the willingness to sign a written informed consent document. 3. ECOG Performance Status 0-2. 4. Histologically confirmed head and neck squamous cell carcinoma of the oropharynx, larynx, hypopharynx, or pharynx. 5. Satisfies eligibility criteria for treatment with concurrent cisplatin with radiation for the definitive treatment of head and neck squamous cell carcinomas. Eligibility criteria are as follows: HPV-negative Stage III-IVB or HPV-positive Stages II-III and select stage I patients as per PI discretion. 6. Adequate organ and marrow function defined as the following: 1. Neutrophils ≥ 1500/μL (in absence of growth factor support) 2. Platelets ≥ 100 x 103/μL without transfusion 3. Hemoglobin ≥ 9.0 g/dL 4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min as determined by Cockcroft-Gault equation 5. Aspartate aminotransferase (AST) ≤ 2.5 x ULN 6. Alanine aminotransferase (ALT) ≤ 2.5 x ULN 7. Direct bilirubin ≤ 1.5 x ULN (except participants with Gilbert's syndrome who must have direct bilirubin ≤ 3 x ULN). 8. WBC count ≥ 2500/μL 9. Lymphocyte count ≥ 500/μL 10. Albumin ≥ 25 g/L (2.5 g/dL)
Exclusion criteria
Participants are excluded from the study if any of the criteria below apply. 1. Prior treatment for head and neck squamous cell carcinoma including systemic therapies, local therapies or radiation. 2. Major medical or other conditions that might affect the study assays: major surgery or trauma in the past 28 days, known current pregnancy, poorly controlled diabetes (repeated glucose \>250), history of or current clinically relevant coagulation abnormalities, as determined by the PI. Tracheostomy and feeding tube placement are permitted at any time. 3. Known additional malignancy within the past 3 years (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma-in-situ that have undergone curative therapy). 4. Active or documented history of autoimmune disease or history of a syndrome that required disease-modifying agents, systemic steroids (\>10 mg prednisone per day or equivalent) or immunosuppressive medications, except for vitiligo, endocrinopathies in participants stable on hormone replacement therapy, or resolved childhood asthma/atopy within the past 2 years. Participants with asthma requiring intermittent use of bronchodilators (such as albuterol) will not be excluded from this study. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiencies) is not considered a form of systemic treatment and is allowed. This
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect on the oral microbiome of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) | Prior to first dose of study drugs, Cycle 2 Day 1 (Day 22), Cycle 3 Day 8 (Day 55), Cycle 7 Day 1 (Day 127) and Cycle 11 Day 1 (Day 211). Each cycle is 21 days. | Changes in shotgun metagenomics sequence analysis of the oral microbiome |
| Effect on imaging correlates of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) | Baseline and month 3 of adjuvant period | Correlation between peripheral immune response and radiographic imaging factors.Correlation between peripheral immune response and radiographic imaging factors. Radiographic imaging outcomes for radiation fibrosis based on ARFI and SWEI will be correlated to 1) proportion of change in peripheral immune cell populations and 2) tissue specimens from dermal wound assay expression fold changes of stromal and immune infiltrating markers (e.g. PCR, IHC). |
| Effect on signaling pathways of immune regulation of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) | Prior to first dose of study drugs, Cycle 1 Day 1 (Day 1), Cycle 2 Day 1 (Day 22), Cycle 3 Day 8 (Day 55)and Cycle 11 Day 1 (Day 211). Each cycle is 21 days. | Measurement of plasma biomarker: soluble CD37 |
| Effect on would healing of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) | Prior to first dose of study drugs and Cycle 3 Day 1 (Day 43). Each cycle is 21 days. | Dermal wound healing assay |
| Effect on fibrosis of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) | Prior to first dose of study drugs, Cycle 7 Day 1 (Day 127) and Cycle 11 Day 1 (Day 211). Each cycle is 21 days. | Quantitative measurements of skin fibrosis using acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) |
| Effect on the cutaneous microbiome of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) | Prior to first dose of study drugs, Cycle 1 Day 1 (Day 1), Cycle 3 Day 1 (Day 43), Cycle 3 Day 8 (Day 55). Each cycle is 21 days. | Changes in shotgun metagenomics sequence analysis of the cutaneous microbiome |
| Incidence of adverse events, summarized by attribute and grade, as assessed by using NCI CTCAE v5.0. | Through 30 days after the last dose of study drug | Toxicity data will be summarized by attribute and grade using NCI CTCAE v5.0. |
| Tolerability of inhibition with concurrent chemoradiation treatment with or without PD1 inhibition and with or without the adenosine 2A receptor (A2AR) and adenosine 2B receptor (A2BR) as measured by incidence of dose limiting toxicities (DLTs). | From first dose of study drug through 4 weeks after the completion of the radiation therapy | Incidence of dose limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median progression-free survival (PFS) | Up to 24 months after the last dose of chemoradiation. | Progression-free survival will be assessed by RECIST 1.1 |
| Proportion of subjects with locoregional recurrence | 1 and 2 years | — |
| Median overall survival | Up to 24 months after the last dose of chemoradiation | — |
| 2-year overall survival | 2 years | — |
| Proportion of subjects who exhibit a response to the study drugs | Up to 24 months after the last dose of chemoradiation. | Response will be assessed by RECIST 1.1 |
Outcome results
None listed