A Study of JNJ-101684362 (HLD-0117) in Patients With Metastatic Breast Cancer

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Breast Cancer

Treatments: Drug: JNJ-101684362 (HLD-0117)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07524855

2026-527749-23-00 (Registry Identifier)

HLD-0117-ONC-101

Details and patient eligibility

About

The purpose of this study is to find out the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of JNJ-101684362 (HLD-0117), to evaluate the safety of JNJ-101684362 (HLD-0117) , and how well the participants can tolerate it in Part 1 (dose escalation) of the study.

Enrollment: 170 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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170 participants in 1 patient group

Arm 1

Experimental group

Description:

JNJ-101684362 (HLD-0117): Participants with estrogen receptor positive (ER+) metastatic breast cancer (MBC) will receive JNJ-101684362 (HLD-0117) orally once daily as monotherapy in Part 1 until recommended dose(s) for expansion has been developed. Participants in Part 2 will receive JNJ-101684362 (HLD-0117) at the RP2Ds developed in Part 1.

Treatment:

Drug: JNJ-101684362 (HLD-0117)