A Study to Assess the Effects of Multiple Study Drug Regimens in Subjects With Newly Diagnosed Locally Advanced Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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A study evaluating the safety, pharmacokinetics, and biomarker profiles of multiple study drugs as monotherapy in subjects with newly diagnosed, treatment-naïve locally advanced squamous cell carcinoma of the head and neck who are candidates for surgical resection.

Official Title
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A Phase 1b Multi-Center Pharmacodynamic Study to Assess the Effects of Multiple Study Drug Regimens in Subjects With Newly Diagnosed Locally Advanced Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: ABBV-181
* Drug: ABBV-368
* Drug: ABBV-927
* Drug: ABBV-927


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed stage 3 to 4B squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx who are candidates for surgical resection and are treatment-naïve. Participants must have been determined to be candidates for surgical resection by a multidisciplinary team including a surgeon, a medical oncologist, and a radiation oncologist. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 and life expectancy of more than 3 months. Must consent to provide the tumor tissues for analyses as described in the protocol. Must have adequate bone marrow function (without any growth factors or transfusions within 2 weeks prior to the first dose), kidney and liver function, with all laboratory values criteria detailed in the protocol. Exclusion Criteria: Has received live vaccine within 28 days prior to the first dose of study drug. Has a history of inflammatory bowel disease, a history of or ongoing pneumonitis or interstitial lung disease, had major surgery ≤ 28 days prior to the first dose of study drug and the surgical wound is not fully healed. Participants with hypopharyngeal or laryngeal tumors will not be candidates for Arm 4 of the study (IT injection of ABBV-927). Requires use of an immunosuppressive medication within 14 days prior to the first dose of the study drug; exceptions are described in the protocol. Has a confirmed positive test results for human immunodeficiency virus, or have active hepatitis A, B or C. Has a history of primary immunodeficiency, allogeneic bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis. Has a history of any other malignancy within the past 3 years except for successfully treated non-melanoma skin cancer or localized carcinoma in situ that is considered cured or adequately treated by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: ABBV-181 IV<br>A single dose of ABBV-181 administered via intravenous (IV) infusion on Day 1. | Drug: ABBV-181<br>* intravenous infusion<br>|
| Experimental: Arm 2: ABBV-368 IV<br>A single dose of ABBV-368 administered via intravenous (IV) infusion on Day 1. | Drug: ABBV-368<br>* intravenous infusion<br>|
| Experimental: Arm 3: ABBV-927 IV<br>A single dose of ABBV-927 administered via intravenous (IV) infusion on Day 1. | Drug: ABBV-927<br>* intravenous infusion<br>|
| Experimental: Arm 4: ABBV-927 IT<br>A single dose of ABBV-927 administered via intratumoral (IT) injection on Day 1. | Drug: ABBV-927<br>* intratumoral injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Gene Expression | The primary biomarker endpoint is to assess immune activation gene changes in the tumor microenvironment associated with T cell infiltration and activation, comparing baseline biopsy to surgical resection following drug treatment. | Baseline (before initiation of drug treatment) and after surgical resection (up to 120 days after study drug administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Serum Concentration (Cmax) of Study Drug | Maximum Serum Concentration (Cmax) of study drug | Up to approximately 120 days | 
| Time to Maximum Plasma Concentration (Tmax) of Study Drug | Time to Maximum Plasma Concentration (Tmax) of study drug | Up to approximately 120 days | 
| Area Under the Plasma Concentration-time Curve of Study Drug in Plasma | Area Under the Plasma Concentration-time Curve (AUC) of study drug in plasma | Up to approximately 120 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Squamous Cell Carcinoma, Cancer, ABBV-927, ABBV-368, ABBV-181, tumor resection, immunotherapeutic drug