Avasopasem plus CDK4/6 inhibitor and hormonal therapy for metastatic HR+, HER2- breast cancer after progression

Phase 1 Clinical Trial of Avasopasem in Patients With Metastatic Hormone Receptor Positive Breast Cancer With Progression on a CDK 4/6 Inhibitor and Hormonal Therapy (CTMS# 24-0096)

This trial tests whether adding avasopasem to a CDK4/6 inhibitor and hormonal therapy is safe and may help people with metastatic HR+, HER2- breast cancer who progressed on prior CDK4/6 plus hormone therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT07137871 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, non-randomized trial giving avasopasem together with a CDK4/6 inhibitor (ribociclib or abemaciclib) and hormonal therapy to patients with metastatic HR+, HER2- breast cancer who progressed on prior CDK4/6 and endocrine therapy. Treatment is delivered in 28-day cycles and tumor response is monitored by CT scans of the chest, abdomen, and pelvis every two cycles. The main focus is on safety, tolerability, and early signs of clinical activity of the combination. Patients must meet specific biomarker and prior-therapy requirements, including ER/PR positivity and prior exposure to ribociclib or abemaciclib (with limited exceptions for prior palbociclib switches for toxicity).

Who should consider this trial

Good fit: Adults with histologically confirmed HR+, HER2- metastatic breast cancer who have progressed on first-line treatment with a CDK4/6 inhibitor (ribociclib or abemaciclib) plus hormonal therapy and meet the study's laboratory and performance criteria are ideal candidates.

Not a fit: Patients with HER2-positive disease, those who progressed while on palbociclib without a subsequent stable period on ribociclib or abemaciclib, or those unable to tolerate combination systemic therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve disease control and extend time on effective systemic therapy for people with metastatic HR+, HER2- breast cancer.

How similar studies have performed: Combining novel agents with CDK4/6 inhibitors is being explored in early-phase research, but adding avasopasem to CDK4/6 inhibitors in this specific setting is largely novel with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* 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.
  * Patients must be ≥ 18 years of age at the time of signing consent.
  * Patients must have an estimated life expectancy of at least 12 weeks.
  * Patients must exhibit an ECOG performance status of 0 or 1.
  * Patients must have adequate organ and bone marrow function as defined below:

    * Leukocytes (WBC) ≥ 3,000/mcL
    * Absolute neutrophil count (ANC) ≥ 1000/mcL
    * Hemoglobin (Hgb) ≥ 7 g/dL
    * Platelets (PLT) ≥ 100,000/mcL
    * Total bilirubin \< 1.5 x Institutional upper limit of normal (ULN); ≤ 3.0 x ULN for patients with Gilbert's syndrome
    * AST (SGOT)/ALT (SGPT) \< 3 x institutional ULN, or \< 5 x ULN if liver metastasis present
    * Creatinine \< 1.5 Institutional ULN
  * Patients with treated brain metastases are eligible if follow-up brain imaging at least 6 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression.
  * Patients must have sufficient samples available to meet Menarini Silicon Biosystems (MSB) specimen requirements.
  * Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  * Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* 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.

Where this trial is running

San Antonio, Texas

• Mays Cancer Center, UT Health San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Kate Lathrop, MD — The University of Texas Health Science Center at San Antonio
• Study coordinator: Kate Lathrop, MD

Conditions Breast Cancer Metastatic; Hormone receptor positive; HR+, HER2 negative metastatic breast cancer; Disease progression