A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The main objective of this study is to assess safety, tolerability, and pharmacokinetics (PK) of ABBV-368 plus tilsotolimod; ABBV-368 plus tilsotolimod and nab-paclitaxel; and ABBV-368 plus tilsotolimod, nab-paclitaxel, and ABBV-181 in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Official Title
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A Phase 1b, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Subjects With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Conditions
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Advanced Solid Tumors Cancer

Intervention / Treatment
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* Drug: ABBV-368
* Drug: Tilsotolimod
* Drug: Nab-paclitaxel
* Drug: ABBV-181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants should weigh at least 35 kg. Eastern Cooperative Oncology Group performance status of 0 or 1 and a life expectancy of >= 3 months. Participant have >= 1 lesion accessible for intratumoral injection. Histologically or cytologically confirmed R/M HNSCC (of the following 4 subsites: oral cavity, oropharynx, larynx, and hypopharynx) who previously progressed either during or after <= 3 prior treatment regimens administered in the recurrent or metastatic setting. Must have received 1 immunotherapy regimen which included a PD-(L)1 inhibitor. Must have received platinum-based therapy, or be considered ineligible for platinum-based therapy by the investigator. Exclusion Criteria: Uncontrolled metastases to the central nervous system (CNS). Participants with brain metastases are eligible provided that evidence of clinical and radiographic stable disease for at least 4 weeks after definitive therapy is given and participants have not used prohibited levels of steroids for at least 4 weeks prior to first dose of the study. Received prior treatment with OX40 or toll-like receptor (TLR) agonists (excluding topical agents).

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-368 + Tilsotolimod<br>Participants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol. | Drug: ABBV-368<br>* Intravenous (IV) infusion<br>Drug: Tilsotolimod<br>* Intratumoral (IT) injection<br>|
| Experimental: Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxel<br>Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol. | Drug: ABBV-368<br>* Intravenous (IV) infusion<br>Drug: Tilsotolimod<br>* Intratumoral (IT) injection<br>Drug: Nab-paclitaxel<br>* Intravenous (IV) infusion<br>|
| Experimental: Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181<br>Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol. | Drug: ABBV-368<br>* Intravenous (IV) infusion<br>Drug: Tilsotolimod<br>* Intratumoral (IT) injection<br>Drug: Nab-paclitaxel<br>* Intravenous (IV) infusion<br>Drug: ABBV-181<br>* Intravenous (IV) infusion<br>* Other names: Budigalimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. | Up to approximately 2 years following the first dose | 
| Change in Vital Signs | Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported. | Up to approximately 2 years following the first dose | 
| Change in Clinical Laboratory Test Results | Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported. | Up to approximately 2 years following the first dose | 
| Maximum Observed Serum Concentration (Cmax) of ABBV-368 | Maximum Serum Concentration (Cmax) of ABBV-368 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Time to Maximum Serum Concentration (Tmax) of ABBV-368 | Time to Maximum Serum Concentration (Tmax) of ABBV-368 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt) | Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt) | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Terminal-Phase Elimination Rate Constant (β) of ABBV-368 | Terminal-Phase Elimination Rate Constant (β) of ABBV-368 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Terminal Half-Life (t1/2) of ABBV-368 | Terminal Half-Life (t1/2) of ABBV-368 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Maximum Plasma Concentration (Cmax) of Tilsotolimod | Maximum Observed Plasma Concentration (Cmax) of Tilsotolimod | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod | Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt) | Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt) | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod | Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Terminal Half-Life (t1/2) of Tilsotolimod | Terminal Half-Life (t1/2) of Tilsotolimod | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Maximum Observed Serum Concentration (Cmax) of ABBV-181 (Arm 3 Only) | Maximum Observed Serum Concentration (Cmax) of ABBV-181 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Time to Maximum Serum Concentration (Tmax) of ABBV-181 (Arm 3 Only) | Time to Maximum Serum Concentration (Tmax) of ABBV-181 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt) (Arm 3 Only) | Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt) | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Terminal-Phase Elimination Rate Constant (β) of ABBV-181 (Arm 3 Only) | Terminal-Phase Elimination Rate Constant (β) of ABBV-181 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 
| Terminal Half-Life (t1/2) of ABBV-181 (Arm 3 Only) | Terminal Half-Life (t1/2) of ABBV-181 | Cycle 1 through Cycle 3 (each cycle is approximately 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is measured as the percentage of participants with a complete response (CR) or partial response (PR) as a confirmed response. | Up to approximately 2 years following the first dose | 
| Clinical Benefit Rate (CBR) | CBR is measured as the percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) | Up to approximately 2 years following the first dose | 
| Time to Response (TTR) | TTR is the time from date of first study drug exposure to the first instance of a complete response (CR) or partial response (PR) as a confirmed response, whichever occurs first. | Up to approximately 2 years following the first dose | 
| Progression Free Survival (PFS) | PFS is the time from date of first study drug exposure to disease progression or death, whichever occurs first. | Up to approximately 2 years following the first dose | 
| Duration of Response (DOR) | DOR is the time from the participant's initial response (CR or PR as a confirmed response) to disease progression or death, whichever occurs first. | Up to approximately 2 years following the first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Locally Advanced Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma, Cancer