A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)

Study Overview
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Brief Summary
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This is an open-label, Phase 1, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-321 for participants with advanced solid tumors likely to overexpress the epidermal growth factor receptor (EGFR). The study will consist of 2 phases: Dose Escalation Phase and Expansion Phase.

Official Title
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A Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)

Conditions
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Advanced Solid Tumors Cancer

Intervention / Treatment
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* Drug: ABBV-321


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Histologically or cytologically confirmed solid tumor of one of the following types associated with overexpression of Epidermal Growth Factor Receptor (EGFR). (For Expansion Phase: Subjects must have EGFR overexpression demonstrated by central assessment or Sponsor selected test). Dose Escalation Phase: Colorectal cancer (CRC), Glioblastoma (GBM), squamous cell carcinoma of the head and neck (HNSCC), non-small cell lung cancer (NSCLC), bladder, cervical, esophageal, kidney or sarcoma. Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent. Participants must not be eligible for, or has refused further therapy that is likely to provide a survival benefit. Must have measureable disease as per RECIST Version 1.1 or RANO (for GBM). Minimum life expectancy of at least 12 weeks. Expansion Phase (Solid Tumor Cohort): Histologically or cytologically confirmed advanced solid tumor. Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent. Must have measureable disease as per RECIST Version 1.1. Minimum life expectancy of at least 12 weeks. Expansion Phase (GBM Cohort Only): Participant has recurrent primary (de novo) glioblastoma histologically confirmed at any time from initial diagnosis through latest recurrence. Participant has recurrent GBM per Response Evaluation in Neuro-Oncology (RANO) requirements. Tumor is measurable according to RANO criteria. Exclusion Criteria: Active uncontrolled infection National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Grade greater than or equal to 3). New York Heart Association (NYHA) Class III or IV heart failure and/or ejection fraction of < 40% as measured by echocardiogram at screening. Unstable angina pectoris or cardiac ventricular arrhythmia. Myocardial infarction or cerebrovascular accident (CVA) within 6 months. Documented history of capillary leak syndrome within 6 months of study enrollment. Grade 2 or higher peripheral edema, ascites, pleural, or pericardial effusion within 4 weeks of study enrollment or any history of recurrent grade 2 or higher effusions requiring ongoing drainage. Active keratitis or current corneal disorder. Laser-assisted in situ keratomileusis (LASIK) procedure within the last 1 year or cataract surgery within the last 3 months. Major surgery (including opening of the abdomen, chest) within 21 days of the first dose of study drug. Uncontrolled metastases from an extracranial solid tumor to the central nervous system (CNS). Participants with brain metastases from an extracranial solid tumor are eligible after definitive therapy provided they are asymptomatic for at least 2 weeks prior to first dose of ABBV-321. No history of medical condition resulting in nephrotic range proteinuria. Participants must not have been treated in anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal therapy, biologic therapy or investigational anti-cancer therapy within a period of 21 days or herbal anticancer therapy within 7 days prior to the first dose of study drug. For approved targeted small molecules, a washout period of 5 half-lives is adequate (no washout period required for subjects currently on erlotinib) Participant must not have been in more than three lines of systemic cytotoxic therapy (excluding adjuvant and neoadjuvant therapy)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-321<br>ABBV-321 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined. | Drug: ABBV-321<br>* Intravenous infusion<br>* Other names: Serclutamab Talirine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCt for ABBV-321 | Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321 | Up to 78 days post dose | 
| AUC∞ for ABBV-321 | AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time. | Up to 78 days post dose | 
| Tmax of ABBV-321 | Time to Cmax (Tmax) of ABBV-321 | Up to 78 days post dose | 
| Terminal phase elimination rate constant (β) for ABBV-321 | Terminal phase elimination rate constant (β) | Up to 78 days post dose | 
| Cmax of ABBV-321 | Maximum observed plasma concentration (Cmax) of ABBV-321 | Up to 78 days post dose | 
| Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321 | The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Phase | Minimum first cycle of dosing (up to 28 days) | 
| t1/2 for ABBV-321 | Terminal elimination half-life (t1/2) | Up to 78 days post dose | 
| Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321 | The MTD of ABBV-321 will be determined during the dose escalation phase of the study. | Minimum first cycle of dosing (up to 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first. | Up to approximately 5 years | 
| Duration of Response (DOR) | DOR for a given participant is defined as the number of days from the day CR or PR (whichever is recorded first) occurred to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first. | Up to approximately 5 years | 
| Disease Control Rate (DCR) | DCR is defined as the proportion of participants with objective evidence of complete response (CR), partial response (PR) or stable disease (SD); a participants best overall response assignment of SD must be maintained for at least 6 weeks since the first dose date of study drug. | Up to 5 years | 
| Time to progression (TTP) | TTP is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST version 1.1 or RANO criteria. | Up to approximately 5 years | 
| Change from Baseline in QTcF | QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline | Up to 61 days post dose | 
| Overall Survival (OS) | OS is defined as number of days from the date of the first dose to the date of death for all dosed participants. For participants who are not deceased, the data will be censored at the last known date to be alive. | Up to approximately 5 years | 
| Objective response rate (ORR) | ORR is defined as the proportion of participants with a response of partial response (PR) or better; Response Assessment in Neuro-Oncology (RANO) criteria will be used for glioblastoma (GBM) participants, and Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria will be used for all other participants. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Advanced Solid Tumors, Epidermal Growth Factor Receptor (EGFR), Squamous cell carcinoma of the head and neck (HNSCC), non-small cell lung cancer (NSCLC), Glioblastoma (GBM), overexpression of Epidermal Growth Factor Receptor (EGFR)