Clinical Trial of Avasopasem in Patients With Metastatic Hormone Receptor Positive Breast Cancer With Progression on a CDK 4/6 Inhibitor and Hormonal Therapy

NCT07137871 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CTMS# 24-0096STUDY00000816
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the safety of avasopasem in combination with CDK 4/6 inhibitor and hormonal therapy in women with metastatic hormone receptor positive breast cancer, and to see if the addition of avasopasem improves the effectiveness of a CDK 4/6 inhibitor and hormonal therapy.

Conditions

Breast Cancer Metastatic

Keywords

Hormone receptor positive; HR+, HER2 negative metastatic breast cancer; Disease progression

Outcome Measures

Primary Outcomes (1)

• Determine Safety and Tolerability of Treatment

  Determine the safety and tolerability of Avasopasem in combination with a CDK 4/6 inhibitor and hormonal therapy. Each cycle of treatment will be 28 days. Toxicity will be assessed starting on the first day of each 28-day treatment cycle, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, and the incidence, nature, and severity of adverse events will be determined.All women who receive at least one dose of Avasopasem will be considered as evaluable for any toxicity and safety endpoints, as well as disease response. Patient reported outcome (PRO's) for adverse events (AE) will also be reported on day one of each cycle.

  Day 1 through Day 28 (each cycle is 28 days, up to 4 months

Secondary Outcomes (1)

• Clinical Benefit Ratio (CBR) with addition of Avasopasem

  Day 1 through Day 28 (each cycle is 28 days, up to 4 months

Other Outcomes (1)

• Patient reported outcomes using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) and EORTC) QLQ-C-30 and EORTC QLC-BR23 a breast cancer-specific quality of life questionnaire

  Day 1 through Day 28 (each cycle is 28 days, up to 4 months

Study Arms (1)

Metastatic Hormone Receptor Positive Breast Cancer

EXPERIMENTAL

This study is investigating the addition of a novel agent, Avasopasem (or GC4419), in patients with hormonal receptor positive (HR+) metastatic breast cancer with progression while on treatment with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor and an aromatase inhibitor.

Drug: Avasopasem

Interventions

Avasopasem DRUG

Avasopasem has also been shown to exhibit both antitumor effects as well as minimal toxicity. Participants are currently taking a CDK 4/6 inhibitor and hormonal therapy

Also known as: GC4419

Metastatic Hormone Receptor Positive Breast Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of HR+, HER2 negative metastatic breast cancer.
• Estrogen receptor (ER) and/or progesterone receptor (PR) expression positivity is defined as at least 10% of tumor cells nuclei positive by immunohistochemistry in the sample on testing.
• HER2 negative: defined as IHC staining of 0 or 1+. If HER2 overexpression is equivocal by IHC, defined as 2+, the tumor must be non-gene amplified by FISH (ratio \<2 and HER2 copy number \<4).
• Progression on treatment with a CDK 4/6 inhibitor and hormonal therapy in the metastatic setting
• The CDK 4/6 inhibitor must be ribociclib or abemaciclib. Patients on palbociclib are not eligible.
• Patient may have been on palbociclib previously but must have been stable on ribociclib or abemaciclib for at least three months prior to enrolling. In this case, the switch from palbociclib to either ribociclib or abemaciclib must have been of toxicity management and not progression of disease.
• Hormonal therapy is defined as an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant.
• Patients on tamoxifen are not eligible.
• Both men and pre/perimenopausal women must be on ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist.
• Patients must have measurable disease based on RECIST 1.1 criteria.
• Females of child-bearing potential (FOCBP) who engage in intercourse must agree to use adequate contraception (e.g., hormonal or an intrauterine device \[IUD\] or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 weeks following completion of therapy.
• NOTE: A FOCBP is any woman who meets the following criteria:
• Has not undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)
• FOCBP must have a negative serum pregnancy test within 7 days prior to registration.

You may not qualify if:

• Patients who have any systemic therapy in the metastatic setting except hormonal therapy in combination with a CDK 4/6 inhibitor. Previously palliative targeted radiation therapy is allowed. Bone targeting agents such as bisphosphonates and rank ligand inhibitors for metastatic breast cancer to the bone is also allowed prior and during this trial.
• Patients with untreated new or progressive brain metastases or leptomeningeal disease
• Use of concomitant nitrates and PDE5 inhibitors.
• Use of potent CYP3A4 inhibitors or inducers and not able to discontinue two weeks prior to enrolling onto the trial.
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints. Note: Patients with HIV or infectious hepatitis must exhibit well controlled disease with stable treatment regimen (where applicable) that in the opinion of the treating physician should not preclude them from participating in the study.
• Patients who are currently pregnant or breast feeding.
• Patients with a history of another invasive malignancy within 2 years of registration with the exception of local squamous cell or basal cell carcinoma of the skin.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Disease Progression

Interventions

avasopasem manganese

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kate Lathrop, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kate Lathrop, MD

CONTACT

210-450-1000; lathrop@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a single institution, non-randomized, phase 1 clinical trial

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 22, 2025
• Study Start: October 2, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (1)