Metastatic Breast Cancer
Conditions
Keywords
breast cancer, RIPTAC, breast carcinoma, locally advanced breast cancer, breast tumor, malignant Tumor of the breast
Brief summary
Assessment of the safety and efficacy of HLD-0117 as monotherapy in patients with estrogen receptor positive (ER+) metastatic breast cancer (MBC) or locally advanced breast cancer that have progressed on prior systemic therapies.
Detailed description
This study is an open-label, dose-escalation and cohort expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of oral single-agent, HLD-0117 in patients with ER+ MBC that have progressed after at least 1 prior systemic line of therapy. During dose escalation, patients will be enrolled into monotherapy cohorts using a Bayesian optimal interval (BOIN) design. Cohorts will enroll a minimum of three patients, with staggered enrollment between cohorts. Backfilling into dose levels determined to be safe may occur to further characterize tolerability and efficacy. The purpose of the study is to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of HLD-0117 as a monotherapy.
Interventions
DRUGHLD-0117
A treatment cycle consists of 28 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking
Intervention model description
Phase 1 dose escalation will employ the BOIN design (to find the Maximum Tolerated Dose (MTD)/ Recommended Dose for Expansion (RDE)). The study enables backfilling patients to doses that are cleared for safety during the dose escalation.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female (assigned at birth), ≥18 years old, and able to provide informed consent * Histologically confirmed metastatic or locally advanced breast cancer * Postmenopausal status defined by surgical or natural menopause, or ovarian suppression with a GnRH agonist * Prior treatment including at least one endocrine therapy in the metastatic setting, at least one CDK4/6 inhibitor (in the adjuvant and/or metastatic setting), and no more than two prior cytotoxic regimens in the metastatic setting * Radiologic disease progression on the most recent therapy * Measurable disease per RECIST v1.1 * Willingness to provide baseline and on-treatment tumor biopsies, unless not feasible or medically appropriate * ER-positive and HER2-negative status documented within 2 years * ECOG performance status 0-1 and life expectancy of at least 3 months * Adequate organ function Recovery from prior therapy-related toxicities to Grade ≤1 (except alopecia; neuropathy and endocrinopathies ≤Grade 2) * Ability to swallow oral medication and comply with study procedures * Stable dose (≥30 days) of bisphosphonates or denosumab, if applicable
Exclusion criteria
* Inflammatory breast cancer or known brain metastases * Recent major bleeding or uncontrolled bleeding disorder * Ongoing corticosteroid use \>10 mg/day (prednisone equivalent) * Recent anticancer or investigational therapy within 14 days (28 days for fulvestrant) * Untreated or unstable spinal cord compression * Significant cardiovascular disease within 6 months or ongoing uncontrolled cardiac conditions * Active or uncontrolled infection (controlled HIV or treated hepatitis C allowed) * Uncontrolled renal, pancreatic, or liver disease (excluding stable conditions such as Gilbert's syndrome or liver metastases) * Another malignancy requiring treatment within 2 years (except low-risk, curatively treated cancers) * Major surgery within 28 days * Any condition that may interfere with safety or study compliance * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | 28 days | Frequency of dose-limiting toxicities (DLTs) |
| AEs, ECGs, Labs and Clinical Changes | 28 days | Frequency and severity of adverse events (AEs) and abnormal electrocardiogram (ECG), laboratory and clinical changes from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 56 Days | Objective response rate (ORR) per RECIST in evaluable patients |
| Duration of response (DOR) | 28 days | Duration of response (DOR) |
| Progression-free survival (rPFS) | 56 days | Radiographic progression-free survival (rPFS) |
| Disease Control Rate (DCR) | 24 weeks | Disease Control Rate (DCR) |
Countries
United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed