A Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)

Study Overview
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Brief Summary
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This is an open-label, Phase I, 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-176 for participants with advanced solid tumors likely to express Prolactin Receptor (PRLR). The study will consist of 2 cohorts: Dose Escalation and Expanded Recommended Phase 2 Dose.

Official Title
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A Phase 1 Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)

Conditions
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Advanced Solid Tumors Cancer

Intervention / Treatment
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* Drug: ABBV-176


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies. Dose Escalation Cohort: must have breast cancer, colorectal cancer, adrenocortical carcinoma, chromophobe renal cell carcinoma. Expanded Cohort: must have breast cancer. Participant must consent to provide the following for biomarker analyses: Dose Escalation Cohort: archived tumor tissue or fresh tumor biopsy. Expanded Cohort: archived tumor tissue and fresh tumor biopsy. Participant has Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Participant has adequate bone marrow, renal, and hepatic function. Exclusion Criteria: Participant received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic, or any investigational therapy within 21 days before Study Day 1; participant received palliative radiotherapy or small molecule targeted anti-cancer agents within 14 days of Study Day 1. Participant has prior exposure to any pyrrolobenzodiazopine-containing agent Participant has unresolved, clinically significant toxicities from prior anticancer therapy, defined as greater than Grade 1 on Common Terminology for adverse events. Participant has clinically significant uncontrolled conditions. Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG). Participant has received more than 4 prior lines of systemic cytotoxic therapy (not including neo-adjuvant or adjuvant therapy). For prior cytotoxic therapy, treatment for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy. Participant has a history of >= grade 3 AST, ALT, or bilirubin increase or has extensive liver resection (i.e., left lobe resection). Participant has a history of cholecystitis (subject with history of cholecystectomy will not be excluded), or has active gallbladder disease.

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: Dose Escalation Cohort<br>ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached. | Drug: ABBV-176<br>* Intravenous infusion<br>|
| Experimental: Expanded RPTD Cohort<br>ABBV-176 via intravenous administration in participants with breast cancer at the Recommended Phase Two Dose (RPTD) determined during the Dose Escalation Cohort | Drug: ABBV-176<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation Cohort: Tmax of ABBV-176 | Time to Cmax (Tmax) of ABBV-176 | Up to approximately 57 days | 
| Dose Escalation Cohort: AUC∞ for ABBV-176 | AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time. | Up to approximately 57 days | 
| Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176 | Terminal phase elimination rate constant (β) | Up to approximately 57 days | 
| Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176 | The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort. | Minimum first cycle of dosing (up to 21 days) | 
| Dose Escalation Cohort: Cmax of ABBV-176 | Maximum observed plasma concentration (Cmax) of ABBV-176. | Up to approximately 57 days | 
| Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176 | MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity. | Minimum first cycle of dosing (up to 21 days) | 
| Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR) | ORR is defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. | Up to approximately 2 years | 
| Dose Escalation Cohort: AUCt for ABBV-176 | Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176. | Up to approximately 57 days | 
| Dose Escalation Cohort: t1/2 for ABBV-176 | Terminal elimination half-life (t1/2) | Up to approximately 57 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded RPTD Cohort: AUCt for ABBV-176 | Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) | Up to approximately 15 days | 
| Expanded RPTD Cohort: Tmax of ABBV-176 | Time to Cmax (Tmax) of ABBV-176 | Up to approximately 15 days | 
| Expanded RPTD Cohort: 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 subjects. For subjects who are not deceased, the data will be censored at the date of the last study visit, or the last know date to be alive, whichever is later. | Up to 2 years after the last dose of study drug | 
| Expanded RPTD Cohort: Cmax of ABBV-176 | Maximum observed plasma concentration (Cmax) of ABBV-176. | Up to approximately 15 days | 
| Expanded RPTD Cohort: Duration of Response (DOR) | DOR is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first. | Up to approximately 2 years | 
| Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176 | Terminal phase elimination rate constant (β) for ABBV-176 | Up to approximately 15 days | 
| Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS) | PFS is defined as the time from the participant's first dose of study drug (Day 1) to the date of documented disease progression (per RECIST 1.1), or death due to any cause, whichever occurs first. | Up to approximately 2 years | 
| Expanded RPTD Cohort: Change in ECOG Performance Status | Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Up to approximately 2 years | 
| Expanded RPTD Cohort: AUC∞ for ABBV-176 | Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC∞) | Up to approximately 15 days | 
| Expanded RPTD Cohort: t1/2 for ABBV-176 | Terminal elimination half-life (t1/2) for ABBV-176 | Up to approximately 15 days | 
| Dose Escalation Cohort: Change from Baseline in QTcF | QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline | Up to approximately 47 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Metastatic, Prolactin Receptor (PRLR), Breast cancer, Colorectal cancer, Adrenocortical carcinoma,, Chromophobe renal cell carcinoma, Hepatocellular carcinoma