Advanced Solid Tumors Cancer
Conditions
Keywords
Cancer, Metastatic, Prolactin Receptor (PRLR), Breast cancer, Colorectal cancer, Adrenocortical carcinoma,, Chromophobe renal cell carcinoma, Hepatocellular carcinoma
Brief summary
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.
Interventions
DRUGABBV-176
Intravenous infusion
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Cohort: Tmax of ABBV-176 | Up to approximately 57 days | Time to Cmax (Tmax) of ABBV-176 |
| Dose Escalation Cohort: AUC∞ for ABBV-176 | Up to approximately 57 days | AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time. |
| Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176 | Up to approximately 57 days | Terminal phase elimination rate constant (β) |
| Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176 | Minimum first cycle of dosing (up to 21 days) | The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort. |
| Dose Escalation Cohort: Cmax of ABBV-176 | Up to approximately 57 days | Maximum observed plasma concentration (Cmax) of ABBV-176. |
| Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176 | Minimum first cycle of dosing (up to 21 days) | MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity. |
| Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR) | Up to approximately 2 years | 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. |
| Dose Escalation Cohort: AUCt for ABBV-176 | Up to approximately 57 days | Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176. |
| Dose Escalation Cohort: t1/2 for ABBV-176 | Up to approximately 57 days | Terminal elimination half-life (t1/2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS) | Up to approximately 2 years | 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. |
| Expanded RPTD Cohort: AUC∞ for ABBV-176 | Up to approximately 15 days | Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC∞) |
| Expanded RPTD Cohort: Change in ECOG Performance Status | Up to approximately 2 years | Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status |
| Expanded RPTD Cohort: t1/2 for ABBV-176 | Up to approximately 15 days | Terminal elimination half-life (t1/2) for ABBV-176 |
| Dose Escalation Cohort: Change from Baseline in QTcF | Up to approximately 47 days | QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline |
| Expanded RPTD Cohort: AUCt for ABBV-176 | Up to approximately 15 days | Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) |
| Expanded RPTD Cohort: Tmax of ABBV-176 | Up to approximately 15 days | Time to Cmax (Tmax) of ABBV-176 |
| Expanded RPTD Cohort: Overall Survival (OS) | Up to 2 years after the last dose of study drug | 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. |
| Expanded RPTD Cohort: Cmax of ABBV-176 | Up to approximately 15 days | Maximum observed plasma concentration (Cmax) of ABBV-176. |
| Expanded RPTD Cohort: Duration of Response (DOR) | Up to approximately 2 years | 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. |
| Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176 | Up to approximately 15 days | Terminal phase elimination rate constant (β) for ABBV-176 |
Countries
Australia, Denmark, Spain, United States
Outcome results
None listed