Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Select Advanced Solid Tumor Indications Receiving Intravenous (IV) ABBV-400

Study Overview
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Brief Summary
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Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors. ABBV-400 is an investigational drug being developed for the treatment of advanced solid tumors. Study doctors put the participants in groups called cohorts. Each cohort receives ABBV-400 alone (monotherapy) followed by a safety follow-up period. Approximately 220 adult participants with hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), esophageal squamous cell carcinoma (ESCC), triple negative breast cancer (TNBC), hormone receptor+/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (hormone receptor-positive [HR+]/HER2-breast cancer [BC]), head and neck squamous-cell-carcinoma (HNSCC), or advanced solid tumors, will be enrolled in the study in approximately 60 sites worldwide. In the each cohorts, participants with the following advanced solid tumor indications: HCC, PDAC, BTC, ESCC, TNBC, HR+/HER2-BC, and HNSCC will receive intravenous (IV) ABBV-400 monotherapy for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Official Title
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A Phase 1 Open-Label Study to Evaluate the Efficacy and Safety of ABBV-400 in Select Advanced Solid Tumor Indications

Conditions
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Hepatocellular Carcinoma, Pancreatic Ductal Adenocarcinoma, Biliary Tract Cancers, Esophageal Squamous Cell Carcinoma, Triple Negative Breast Cancer, Hormone Receptor+/Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer, Head and Neck Squamous-Cell Carcinoma

Intervention / Treatment
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* Drug: ABBV-400


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Laboratory values meeting the criteria laid out in the protocol. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Documented diagnosis of locally advanced or metastatic hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), squamous cell carcinoma of the esophagus, (ESCC), triple negative breast cancer (TNBC), hormone receptor+/HER2-breast cancer (HR+/HER2-BC), or head and neck squamous-cell-carcinoma (HNSCC) (by World Health Organization [WHO] criteria). Participant meets the criteria for disease activity laid out in the protocol. Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at screening (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), and prior pneumonectomy. Exclusion Criteria: Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-400. Palliative radiation therapy for bone, skin, or subcutaneous metastases with 10 fractions or less is permitted and not subject to a washout period. Unresolved AEs > Grade 1 from prior anticancer therapy except for alopecia. History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis, including but not limited to those listed in the protocol. History of clinically significant, intercurrent lung-specific illnesses, including those laid out in the protocol. Untreated brain or meningeal metastases (i.e., participants with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy). Participants may continue on antiepileptic therapy if required. History of other active malignancy, with the exception of those laid out in the protocol

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Hepatocellular Carcinoma (HCC)<br>Participants with HCC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Cohort 2: Pancreatic Ductal Adenocarcinoma (PDAC)<br>Participants with PDAC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Cohort 3: Biliary Tract Cancers (BTC)<br>Participants with BTC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Cohort 4: Esophageal Squamous Cell Carcinoma, (ESCC)<br>Participants with ESCC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Cohort 5: Triple Negative Breast Cancer (TNBC)<br>Participants with TNBC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Cohort 6: Hormone Receptor+/HER2-breast Cancer (HR+/HER2-BC)<br>Participants with HR+/HER2-BC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Cohort 7: Head and Neck Squamous-cell-carcinoma (HNSCC)<br>Participants with HNSCC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR defined as percentage of participants with confirmed best overall response of confirmed partial response (PR) or better per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Up to 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) for Participants with Confirmed Complete Response (CR)/PR | DOR is defined for participants achieving a confirmed PR or better as the time from the initial response of PR (or better) per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier. | Up to 24 Months | 
| Clinical Benefit Rate | CBR is defined as the proportion of participants with a best overall response of stable disease at least 5 weeks post first dose, confirmed CR or PR per investigator review according to RECIST, version 1.1 | Up to 24 Months | 
| Progression-free Survival (PFS) | PFS is defined as time from first study treatment to a documented disease progression according to RECIST, version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier. | Up to 24 Months | 
| Overall Survival (OS) | OS is defined as time from first study treatment to death due to any cause. | Up to 24 Months | 
| Maximum Observed Concentration (Cmax) of ABBV-400 | Cmax of ABBV-400. | Up to 24 Months | 
| Time to Cmax (Tmax) of ABBV-400 | Tmax of ABBV-400. | Up to 24 Months | 
| Area Under the Plasma Concentration-time Curve (AUC) for Total Antibody Concentration | AUC for total antibody concentration. | Up to 24 Months | 
| Total Antibody Drug Conjugate (ADC) Concentration | Total ADC concentration. | Up to 24 Months | 
| Plasma Concentrations of Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload | Plasma concentrations of unconjugated Top1 inhibitor payload. | Up to 24 Months | 
| Antidrug Antibody (ADA) | Incidence and concentration of anti-drug antibodies. | Up to 24 Months | 
| Neutralizing Antidrug Antibody (nADA) | Incidence and concentration of neutralizing anti-drug antibodies. | Up to 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Pancreatic Ductal Adenocarcinoma, Biliary Tract Cancers, Esophageal Squamous Cell Carcinoma, Triple Negative Breast Cancer, Hormone Receptor+/Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer, Head and Neck Squamous-Cell Carcinoma, Solid Tumors, Advanced Solid Tumors, ABBV-400