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

NCT04892875 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: VICC-VCHAN23126P
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (11)

• Incidence of adverse events, summarized by attribute and grade, as assessed by using NCI CTCAE v5.0.

  Toxicity data will be summarized by attribute and grade using NCI CTCAE v5.0.

  Through 30 days after the last dose of study drug

• 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).

  Incidence of dose limiting toxicities (DLTs)

  From first dose of study drug through 4 weeks after the completion of the radiation therapy

• 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)

  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).

  Baseline and month 3 of adjuvant period

• 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)

  Measurement of plasma biomarker: soluble CD37

  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.

• 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)

  Measurement of plasma biomarker: cytokines

  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.

• 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)

  Measurement of plasma biomarker: chemokines

  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.

• 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)

  Measurement of plasma biomarker: peripheral blood mononuclear cells (PBMCs)

  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.

• 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)

  Dermal wound healing assay

  Prior to first dose of study drugs and Cycle 3 Day 1 (Day 43). Each cycle is 21 days.

• 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)

  Quantitative measurements of skin fibrosis using acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI)

  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.

• 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)

  Changes in shotgun metagenomics sequence analysis of the cutaneous microbiome

  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.

• 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)

  Changes in shotgun metagenomics sequence analysis of the oral microbiome

  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.

Secondary Outcomes (5)

• Proportion of subjects who exhibit a response to the study drugs

  Up to 24 months after the last dose of chemoradiation.

• Median progression-free survival (PFS)

  Up to 24 months after the last dose of chemoradiation.

• 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

Study Arms (3)

Concurrent Cisplatin/Radiation Therapy + Zimberelimab (Cohort 1)

EXPERIMENTAL

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

Drug: Zimberelimab; Drug: Cisplatin; Radiation: Radiation

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

EXPERIMENTAL

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

Drug: Zimberelimab; Drug: Etrumadenant; Drug: Cisplatin; Radiation: Radiation

Concurrent Cisplatin/Radiation Therapy

ACTIVE COMPARATOR

Concurrent weekly cisplatin with radiation therapy control arm

Drug: Cisplatin; Radiation: Radiation

Interventions

Zimberelimab 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.

Also known as: AB122

Concurrent Cisplatin/Radiation Therapy + Zimberelimab (Cohort 1); Concurrent Cisplatin/Radiation Therapy + Zimberelimab + Etrumadenant (Cohort 2)

Etrumadenant 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.

Also known as: AB928

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

Cisplatin 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.

Concurrent Cisplatin/Radiation Therapy; Concurrent Cisplatin/Radiation Therapy + Zimberelimab (Cohort 1); Concurrent Cisplatin/Radiation Therapy + Zimberelimab + Etrumadenant (Cohort 2)

Radiation 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 Cisplatin/Radiation Therapy + Zimberelimab (Cohort 1); Concurrent Cisplatin/Radiation Therapy + Zimberelimab + Etrumadenant (Cohort 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the criteria below apply.
• Age ≥ 18 years of age.
• Ability to understand and the willingness to sign a written informed consent document.
• ECOG Performance Status 0-2.
• Histologically confirmed head and neck squamous cell carcinoma of the oropharynx, larynx, hypopharynx, or pharynx.
• 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.
• Adequate organ and marrow function defined as the following:
• Neutrophils ≥ 1500/μL (in absence of growth factor support)
• Platelets ≥ 100 x 103/μL without transfusion
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min as determined by Cockcroft-Gault equation
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Direct bilirubin ≤ 1.5 x ULN (except participants with Gilbert's syndrome who must have direct bilirubin ≤ 3 x ULN).
• WBC count ≥ 2500/μL

You may not qualify if:

• Participants are excluded from the study if any of the criteria below apply.
• Prior treatment for head and neck squamous cell carcinoma including systemic therapies, local therapies or radiation.
• 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.
• 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).
• 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.
• History of myocardial infarction within 6 months or history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
• Known infection with hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV).
• 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.
• Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment.
• Cohort 2 only: Inability to swallow medications.
• Cohort 2 only: Malabsorption condition that would alter the absorption of orally administered medications.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Jennifer Choe: lead
• Arcus Biosciences, Inc.: collaborator

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Pharyngeal Neoplasms; Hypopharyngeal Neoplasms

Interventions

zimberelimab; Cisplatin; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Mouth Diseases; Stomatognathic Diseases; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Physical Phenomena

Study Officials

• Jennifer Choe, MD, PhD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 19, 2021
• Study Start: December 31, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share