A Study of Concurrent Chemoradiation in Combination With or Without PD1 Inhibitor AB122 Adenosine 2a Receptor / Adenosine 2b Receptor Inhibitor AB928 Therapies in Locally Advanced Head and Neck Cancers

NCT ID: NCT04892875

Last Updated: 2023-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-31

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Concurrent Cisplatin/Radiation Therapy + Zimberelimab (Cohort 1)

Concurrent weekly cisplatin with radiation and zimberelimab therapy followed by adjuvant zimberelimab

Group Type EXPERIMENTAL

Zimberelimab

Intervention Type DRUG

Zimberelimab will be administered at a dose of 360 mg IV on Day 1 of each 21-day cycle for up to 11 cycles.

Cisplatin

Intervention Type DRUG

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.

Radiation

Intervention Type RADIATION

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.

Concurrent Cisplatin/Radiation Therapy + Zimberelimab + Etrumadenant (Cohort 2)

Concurrent weekly cisplatin with radiation + etrumadenant + zimberelimab with adjuvant combined etrumadenant + zimberelimab

Group Type EXPERIMENTAL

Zimberelimab

Intervention Type DRUG

Zimberelimab will be administered at a dose of 360 mg IV on Day 1 of each 21-day cycle for up to 11 cycles.

Etrumadenant

Intervention Type DRUG

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.

Cisplatin

Intervention Type DRUG

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.

Radiation

Intervention Type RADIATION

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.

Concurrent Cisplatin/Radiation Therapy

Concurrent weekly cisplatin with radiation therapy control arm

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

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.

Radiation

Intervention Type RADIATION

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.

Interventions

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Zimberelimab

Zimberelimab will be administered at a dose of 360 mg IV on Day 1 of each 21-day cycle for up to 11 cycles.

Intervention Type DRUG

Etrumadenant

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.

Intervention Type DRUG

Cisplatin

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.

Intervention Type DRUG

Radiation

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.

Intervention Type RADIATION

Other Intervention Names

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AB122 AB928

Eligibility Criteria

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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).
5. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring systemic antibiotic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the Investigator or PI.
6. History of myocardial infarction within 6 months or history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
7. Known infection with hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV).
8. History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
9. Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment.
10. Cohort 2 only: Inability to swallow medications.
11. Cohort 2 only: Malabsorption condition that would alter the absorption of orally administered medications.
12. Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation); INR or aPTT ≥ 1.5 ULN.
13. Use of medications that are likely to significantly affect wound healing or clotting (e.g. steroids, anti-coagulants, aspirin \> 325 mg per day or other NSAID more once per day).
14. Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

a. Topical antibiotics are not permitted within 24 hours from the collection "Skin biopsy Pair 1" if the areas of application are anticipated to interfere with the anticipated sites of biopsies.
15. Use of systemic steroids \>10 mg prednisone (or equivalent) within 7 days prior to the collection of "Skin biopsy Pair 1" with the exception of pulse dose steroids the day prior to and after CT for prevention of a contrast allergy.
16. Use of any live attenuated vaccines against infectious diseases (e.g., influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
17. Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other immune checkpoint inhibitor or agonist as monotherapy or in combination.
18. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before investigational product administration.

In addition, participants are excluded from Cohort 2 if any of the criteria below apply.
19. Prior treatment with an agent targeting the adenosine pathway.
20. Treatment with known breast cancer resistance protein (BCRP) substrates with a narrow therapeutic window, administered orally (eg, prazosin, rosuvastatin) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
21. Treatment with known P-glycoprotein (P-gp) substrates with a narrow therapeutic window, administered orally (eg, digoxin) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
22. Treatment with known strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half lives of the drug (whichever is longer) prior to initiation of study treatment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role collaborator

Jennifer Choe

OTHER

Sponsor Role lead

Responsible Party

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Jennifer Choe

Assistant Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Jennifer Choe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Countries

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United States

Other Identifiers

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VICC-VCHAN23126P

Identifier Type: -

Identifier Source: org_study_id