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

Immunologic Targeting of Native and Mutated ESR1 Receptor for Treatment of Hormone Receptor Expressing Metastatic Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: HER2-negative Breast Cancer; Breast Cancer Metastatic Breast Cancer
• Intervention / Treatment: Drug: Elacestrant; Biological: DC1 native/mutated ESR1

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Aixa Soyano Muller, MD; Email: Aixa.Soyano@moffitt.org
• Study Contact Backup: Name: Taylor Lewis Whann; Phone Number: 813-745-0824; Email: Taylor.LewisWhann@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Sub-Investigator: Christine Laronga, MD
      • Sub-Investigator: Heather S Han, MD
      • Sub-Investigator: Mohammed Al-Jumayli, MD
      • Sub-Investigator: Brian Czerniecki, MD, PhD
      • Sub-Investigator: Avan Armaghani, MD
      • Sub-Investigator: Christine Sam, MD
      • Principal Investigator: Aixa Soyano Muller, MD
      • Sub-Investigator: Ricardo Costa, MD
      • Sub-Investigator: Martine Extermann, MD
      • Sub-Investigator: Susan J Hoover, MD
      • Sub-Investigator: Nazanin Khakpour, MD, F.A.C.S.
      • Sub-Investigator: John Kiluk, MD
      • Sub-Investigator: Laura Kruper, MD
      • Sub-Investigator: Marie C Lee, MD
      • Sub-Investigator: Loretta S Loftus, MD
      • Sub-Investigator: Melisssa Mallory, MD
      • Sub-Investigator: Tracey O'Connor, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

  1. Estrogen Receptor (ER) or Progesterone Receptor (PR) are considered positive when expressed ≥1% on immunohistochemistry (IHC).
  2. 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:

  1. absolute neutrophil count ≥1,000/mcL
  2. 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.
• Participants that are pre-menopausal women of childbearing potential who are sexually active with a male partner must agree to use adequate contraception prior to the study, for the duration of study participation.
• Inclusion of minorities: patients of all races and ethnic groups who meet the above inclusion and below exclusion criteria are eligible for this trial.
• 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.

Exclusion Criteria:

• 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.

• 14 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.
• Patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HbsAg]), or hepatitis C (HCV). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible. Participants with positive Hepatitis C Virus (HCV) antibody are eligible if polymerase chain reaction is negative for HCV RNA.
• Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study drugs, with the following exceptions: premedication with dexamethasone, intranasal, inhaled, topical or local steroid injections, systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before CT scan).
• Inability to comply with protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Elacestrant + DC1; 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; 345 mg (or 86 mg tablets) orally daily during vaccination and continued after until progression. Cycle Length 28 days (4 weeks); Other Names: Oserdu; Biological: DC1 native/mutated ESR1; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression Free Survival (PFS) is measured from the start of treatment until disease progression or death from any cause.	Up to 2 years
Clinical Benefit Rate (CBR)	Clinical Benefit Rate (CBR) is measured by Complete Response (CR) + Partial Response (PR) + Stable Disease.	Up to 2 years
Overall Response Rate (ORR)	Overall Response Rate (ORR) is measured by Complete Response (CR) + Partial Response (PR).	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	Dose limiting toxicity (DLT) is defined as grade ≥ 3 non-hematologic toxicity; grade ≥ 3 hematologic toxicity thought be at least possibly related to vaccines. Toxicity data will be reviewed after small groups of patients have been treated and observed for 30 days after the last vaccination. The study will enroll a total number of 18 patients. Enrollment will be suspended if data suggest that the rate of unacceptable vaccine-related toxicity exceeds 25%.	Up to 2 years

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: The V Foundation for Cancer Research
• Investigators: Principal Investigator: Aixa Soyano Muller, MD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic Breast Cancer; HER-2 Negative Breast Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; elacestrant
• Other Study ID Numbers: MCC-23161

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No