Immunologic Targeting of ESR1 Receptor for Hormone Receptor Expressing Metastatic Breast Cancer

NCT06691035 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MCC-23161
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to determine feasibility and safety of the combination of Dendritic Cell (DC1) vaccines and elacestrant in patients with hormone positive HER2 negative metastatic breast cancer.

Conditions

HER2-negative Breast Cancer; Breast Cancer Metastatic Breast Cancer

Keywords

HER-2 Negative Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Rate of Successful Completion

  Feasibility: Defined as a patient's ability and willingness to complete the treatment regimen (8 weeks) to End of Treatment (EOT) (window of + 30 days from date of last study treatment). Data collection will include rate of successful completion.

  Up to 2 years

• Occurrence Rate

  Feasibility: Defined as a patient's ability and willingness to complete the treatment regimen (8 weeks) to End of Treatment (EOT) (window of + 30 days from date of last study treatment). Data collection will include occurrence rate for each reason stated for non-completion.

  Up to 2 years

• Occurrence of Treatment Related Adverse Events

  Number of participants with treatment related adverse events, per event category.

  Up to 2 years

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Up to 2 years

• Clinical Benefit Rate (CBR)

  Up to 2 years

• Overall Response Rate (ORR)

  Up to 2 years

Other Outcomes (1)

• Dose Limiting Toxicity

  Up to 2 years

Study Arms (1)

Elacestrant + DC1

EXPERIMENTAL

Patients will undergo apheresis of peripheral blood to collect and create DC1 vaccines. DC1 will be pulsed with ESR1 native or mutated peptides. After DC1 vaccines have undergone safety testing and are ready to be used, patients will be injected in groin nodes (or accessible breast tumor if available) weekly with these pulsed DC1 for eight consecutive weeks. They will alternate between native ESR1 DC1s and mutated ESR1 DC1s. Patients will receive combination of DC1 vaccinations and Elacestrant concurrently. Elacestrant is a novel oral selective estrogen downregulator, administered during vaccination and continued after. Elacestrant is considered standard of care for patients with ESR1 mutated HR+ HER2-metastatic breast cancer. Pulsed DC1 will be administered after initial induction every four weeks x 3 doses.

Drug: Elacestrant; Biological: DC1 native/mutated ESR1

Interventions

Elacestrant DRUG

345 mg (or 86 mg tablets) orally daily during vaccination and continued after until progression. Cycle Length 28 days (4 weeks)

Also known as: Oserdu

Elacestrant + DC1

DC1 native/mutated ESR1 BIOLOGICAL

2.0-5.0 x 10 (20-50 million) cells (Injections in groin nodes (or accessible breast tumor if available) weekly with DC1 for eight consecutive weeks, alternating between native ESR1 DC1s and mutated ESR1 DC1s. Mutated ESR1 DC1s on week 1 followed by native ESR1 DC1s on week 2, alternating during the initial vaccination series and the subsequent booster phase. Pulsed DC1 will be administered after initial induction every four weeks x 3 doses.

Elacestrant + DC1

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed diagnosis of hormone positive HER2 negative metastatic breast cancer per ASCO/CAP criteria, with diagnosis established through either a breast/axillary biopsy or biopsy of a metastatic lesion.
• Estrogen Receptor (ER) or Progesterone Receptor (PR) are considered positive when expressed ≥1% on immunohistochemistry (IHC).
• HER2 is considered negative by IHC when expression is 0 or 1+ and if equivocal 2+ then a reflex in situ hybridization should be not amplified (standard practice per ASCO/CAP criteria).
• Participants must have Presence of an ESR1 mutation detected via tissue based or blood based (ctDNA) genomic profiling.
• Participants must have been previously treated with at least 1 line of endocrine therapy and a CDK 4/6 inhibitor in the metastatic setting.
• Participants must have measurable or nonmeasurable (evaluable) disease on imaging by RECIST v1.1.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Participants must be adults 18 years or older.
• Participants must have the ability to understand and the willingness to sign a written informed consent document.
• Participants must be able to read and speak standard English or Spanish.
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥75,000/mcL
• d. AST(SGOT)/ALT(SGPT) ≤3 fold × institutional ULN e. creatinine 1.5 ≤ institutional ULN f. hemoglobin (Hb) ≥ 9 g/dL g. Total bilirubin \< 1.5 x ULN or \<3 x ULN in the presence of documented Gilbert's syndrome unconjugated hyperbilirubinemia)
• Participants must have a negative pregnancy test for pre-menopausal women of childbearing potential.

You may not qualify if:

• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Participants must have the ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the participant's behalf.
• Participants with treated and stable brain metastases are eligible if brain imaging shows no evidence of progression within 2 months of trial enrollment.
• Pregnant women are excluded from this study because study treatment agent(s) used in this study may have the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with agents used in this study, breastfeeding should be discontinued if the mother is treated with study agents used in this study.
• Previous treatment with Elacestrant.
• History of allergic reactions attributed to the study drugs.
• Active, progressing or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, because systemic treatment would need to be paused for these patients.
• Treatment with any investigational compound within 21 days prior to the first dose of study drugs or during this study.
• day washout periods from previous anticancer therapy(ies) is required prior to enrollment including:
• Cytotoxic chemotherapy
• Tamoxifen or aromatase inhibitors
• Fulvestrant
• Targeted agents such as CDK 4/6 inhibitors, PIK3CA inhibitors, MTOR inhibitors
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Uncontrolled intercurrent illness including-but not limited to-ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• The V Foundation for Cancer Research: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Aixa Soyano Muller, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Taylor Lewis Whann

CONTACT

813-745-0824; Taylor.LewisWhann@moffitt.org

Aixa Soyano Muller, MD

CONTACT

Aixa.Soyano@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2024
• First Posted: November 15, 2024
• Study Start: November 4, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

US (1)