HLD-0117 treatment for ER-positive metastatic breast cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is an open-label, first-in-human phase 1 study of oral HLD-0117 given as a single agent to patients with estrogen receptor–positive, HER2-negative metastatic or locally advanced breast cancer after prior systemic therapy. The trial uses a Bayesian optimal interval (BOIN) dose-escalation design with cohorts of at least three patients and allows backfilling into dose levels found to be safe, followed by cohort expansion at recommended doses. Key measurements include safety and tolerability, determination of the maximum tolerated dose and/or recommended dose(s) for expansion, pharmacokinetics and pharmacodynamics, and preliminary anti-tumor activity by RECIST v1.1. Mandatory baseline and on-treatment tumor biopsies are requested when feasible to support biomarker and PD assessments.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Female (assigned at birth), greater than or equal to (\>=) 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 therapy including

  1. Must have received at least one endocrine therapy in the metastatic setting.
  2. Must have received at least one cyclin-dependent kinase (CDK) 4/6i, either in the adjuvant and/or metastatic setting.
  3. For Part 1 and Part 2 Cohorts 2A, 2B, 2C, and 2D: Participants may have received up to two prior distinct cytotoxic regimens (for example, taxanes, antibody-drug conjugates (ADCs), etc.) in the metastatic setting, unless discussed and approved by the medical monitor.
  4. For Part 2 Cohort 2E: Participants must have received more than two prior distinct cytotoxic regimens (for example, taxanes, ADCs, etc.) in the metastatic setting.
* Radiologic disease progression on the most recent therapy
* Patients must have disease evaluable per response evaluation criteria in solid tumors (RECIST) v1.1

  1. For Part 1 and Part 2B, 2C, and 2E: Participants may have either evaluable or measurable disease per RECIST v1.1.
  2. For Part 2 Cohort 2A: Participants should have measurable soft tissue disease per RECIST v1.1.
  3. For Part 2 Cohort 2D: Participants should have evaluable but not measurable disease.
* Willingness to provide baseline and on-treatment tumor biopsies, unless not feasible or medically appropriate
* For Part 1 and Part 2 (all cohorts):

  1. Participants must have documented \>=10% ER staining and human epidermal growth factor receptor 2 (HER2) negative (per american society of clinical oncology \[ASCO\] college of american pathologists \[CAP\] guidelines) on the most recent tumor biopsy sample obtained.
  2. For Part 2 Cohort 2B: Participants must have recent estrogen receptor 1 gene (ESR1) wild type from tumor or circulating tumor deoxy ribonucleic acid (ctDNA) testing performed after the most recent endocrine therapy prior to enrollment.
  3. For Part 2 Cohort 2C: Participants must have ESR1 mutation detected from tumor or ctDNA testing performed prior to enrollment.
* Eastern cooperative oncology group (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:

* Participants with Inflammatory breast cancer or leptomeningeal disease or brain metastases, with the exception of patients with definitively treated brain metastases that are clinically stable and asymptomatic for \>2 weeks and who are off or receiving low-dose corticosteroid treatment (\<=10 mg prednisone or equivalent) for at least 2 weeks prior to start of study treatment.
* 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

Where it's running

• Yale University School Of Medicine
  New Haven, Connecticut, United States Recruiting
• Florida Cancer Specialists
  Sarasota, Florida, United States Recruiting
• Massachusetts General Hospital
  Boston, Massachusetts, United States Recruiting
• SCRI Oncology Partners
  Nashville, Tennessee, United States Recruiting
• South Texas Accelerated Research Therapeutics, LLC (START)
  San Antonio, Texas, United States Recruiting
• Next Virginia
  Fairfax, Virginia, United States Recruiting

Study contacts

• Study coordinator: Study Contact
• Email: Participate-In-This-Study1@its.jnj.com
• Phone: 844-434-4210

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.