Individualized vaccine for HR+ breast cancer

Converting HR+ Breast Cancer Into an Individualized Vaccine

This study is testing a personalized vaccine combined with standard hormone therapy and radiation to see if it can help newly diagnosed post-menopausal women with a specific type of breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 90 Years
• Sex: Female
• Sponsor: Weill Medical College of Cornell University (Academic / other)
• Drugs / interventions: pembrolizumab, chemotherapy, prednisone, immunotherapy, radiation
• Locations: 8 sites (Los Angeles, California and 7 other locations)
• Trial ID: NCT03804944 on ClinicalTrials.gov

What this trial studies

This clinical trial involves newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer who will receive 4 months of standard neoadjuvant hormonal therapy with letrozole. Participants will be randomly assigned to one of four treatment arms, which include combinations of focal radiation therapy and immunotherapy options such as pembrolizumab or FLT3L. The study spans a total of 5 months, including a follow-up period after breast surgery. The aim is to evaluate the effectiveness of these treatments in converting breast cancer into a more manageable condition.

Who should consider this trial

Good fit: Ideal candidates are post-menopausal women aged 18 and older with biopsy-proven ER+ PR+ or PR- HER2- breast cancer at clinical stage II-III.

Not a fit: Patients with non-HR+ breast cancer or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more personalized and effective treatment options for patients with HR+ breast cancer.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

* Post-menopausal female ≥ 18 years of age (Post-menopausal status defined as either 1) at least 2 years without menstrual period or 2) or patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Biopsy proven diagnosis of ER+ PR+ or PR- HER2- breast cancer.
* Clinical stage I(\>1.5cm, if N0) - III breast cancer, as per AJCC staging 8th edition.
* Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document.

Adequate bone marrow reserve and liver function:

WBC ≥ 2000/uL Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100 000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

* Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy
* Current use of systemic chemotherapy, endoctine therap or HER2-neu targeted therapy
* Post surgical excision of breast cancer.
* Previous radiotherapy of the same breast.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
* Inability to obtain histologic proof of breast cancer
* Has received a live vaccine within 30 days prior to the first dose of study drug.

Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy (second primary) that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
* Has a known history of active TB (Bacillus Tuberculosis). Note: optional based on country.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Where this trial is running

Los Angeles, California and 7 other locations

• Cedars-Sinai Medical Center — Los Angeles, California, United States (Withdrawn)
• Icahn School of Medicine at Mt Sinai — New York, New York, United States (Withdrawn)
• New York Presbyterian Hospital - Queens — New York, New York, United States (Recruiting)
• Weill Cornell Medicine New York Presbyterian Hospital — New York, New York, United States (Recruiting)
• Brooklyn Methodist Hospital - NewYork Presbyterian — New York, New York, United States (Recruiting)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Withdrawn)
• UT Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• Houston Methodist Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Silvia Formenti, M.D. — Weill Cornell Medicine - New York Presbyterian Hospital
• Study coordinator: Fabiana Gregucci, M.D.

Conditions Breast Cancer