Establishing the Recommended Biological Dose for AE37 Peptide Vaccine in Combination With Pembrolizumab That Will Enhance the Tumor-specific Immune Response and Demonstrate Efficacy in Patients With Advanced Triple-negative Breast Cancer

NCT04024800 | Unknown Phase 2 FDA Drug

• 2 other identifiers: NSABP FB-14MK3475 KN 548
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 6

Brief Summary

This study will look to establish the recommended biologic dose of AE37 in combination with pembrolizumab that will enhance the tumor-specific immune response and demonstrate efficacy in patients with advanced triple-negative breast cancer. This study will take place in two parts. Stage 1 will be the safety cohort (13 patients) to determine the recommended dose of AE37 vaccine that can safely be administered with pembrolizumab. Stage 2 will be an expansion cohort (16 patients) that will consist of the recommended dose of AE37 determined in Stage 1.

Conditions

Triple-negative Breast Cancer

Keywords

Triple-negative Breast Cancer; Tumor-specific immune response; Open-Label; Pembrolizumab; Peptide vaccine; Metastatic Breast Cancer; Dose limiting toxicity; RECIST 1.1; AE37

Outcome Measures

Primary Outcomes (2)

• Recommended dose

  Recommended dose of AE37 that can be safely administered with pembrolizumab. If dose limiting toxicities occur in 4 of the first 13 patients the study therapy vaccine dose will be de-escalated to 500 micrograms (dose-level 1). If fewer than 4 patients experience DLTs then the expansion cohort of 16 patients will be added.

  Day 1, within 72 hours of vaccination (48-72 hours), and as adverse events occur in each cycle (21 days) of study therapy (first 13 patients).

• Objective response rate

  Objective response rate determined by RECIST 1.1 with modifications for progressive disease confirmation

  From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) )or two years.

Secondary Outcomes (4)

• Progression-free Survival

  From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years.

• Overall Survival

  From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years.

• Clinical benefit rate

  From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years.

• Overall Toxicity

  Adverse events assessed from the beginning of study therapy through 90 days after the last dose of study therapy

Study Arms (1)

Arm 1

EXPERIMENTAL

AE37 peptide vaccine every 21 days for 5 doses + Pembrolizumab every 21 days for 2 years (Maximum 35 cycles)

Biological: AE37 Peptide vaccine; Biological: Pembrolizumab

Interventions

AE37 Peptide vaccine BIOLOGICAL

Starting dose: AE37 vaccine 1000 micrograms split into 2 doses given as intradermal injection on day 1 of every 3 week cycle (21 day cycle) for 5 cycles. Should ≥ grade 3 systemic toxicities (DLT) occur in \> 25% (4) of the first 13 patients (4 or more) the study therapy vaccine dose will be de-escalated to 500 micrograms (dose level -1).

Also known as: AE37

Arm 1

Pembrolizumab BIOLOGICAL

Pembrolizumab 200 mg IV on day 1 of every 3 week cycle (21 day cycle) for 2 years (35 cycles)

Also known as: MK-3475

Arm 1

Eligibility Criteria

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

You may qualify if:

• Have a performance status of 0 or 1 on the (Eastern Cooperative Oncology Group) ECOG Performance Scale.
• Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast.
• The primary or metastatic tissue must be triple-negative (ER/PR less than or equal to 9%, HER2-negative \[human epidermal growth factor receptor 2\] by American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines).
• There must be documentation that the patient has evidence of measurable metastatic breast cancer based on RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Histologic confirmation of metastatic disease is not required.
• At least 1 of the tumor sites must be amenable to core needle biopsy.
• Patients with treated, stable, asymptomatic metastatic disease to the brain not requiring chronic corticosteroids are eligible (per discretion of the treating investigator).
• Patient must have resolution of toxic effect(s) of the most recent chemotherapy less than or equal to Grade 1 (except alopecia). If the patient has received major surgery or radiation therapy of greater than 30 Gy, they must have recovered from the toxicity and/or complication from the intervention.
• Demonstrate adequate organ function, all screening labs should be performed within two weeks of treatment initiation.
• ANC (absolute neutrophil count) count greater than or equal to 1,500/mm3
• Platelets greater than or equal to 100,000/mm3
• Hemoglobin greater than or equal to 9 g/dL
• Creatinine less than or equal to 1.5x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) greater than or equal to 30mL/min for patients with creatinine levels greater than 1.5x institutional ULN. (Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl.)
• Total bilirubin less than or equal to 1.5x ULN OR Direct bilirubin less than or equal to ULN for patients with total bilirubin levels greater than 1.5 x ULN.
• AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN OR less than or equal to 5 x ULN for patients with liver metastases.
• A less than or equal to Grade 2 skin reaction to the first DTH inoculation is required to begin study therapy.

You may not qualify if:

• Greater than 1 line of therapy for metastatic disease. Note: patients presenting with stage IV disease should have one line of standard therapy.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids must be discussed with the NSABP Department of Site and Study Management (DSSM).
• A greater than Grade 2 skin reaction to the first DTH inoculation will exclude that patient from beginning study therapy.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Patients with alopecia are an exception to this criterion and may qualify for the study.
• Blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to beginning study therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancers.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• Has an active autoimmune disease that has required systemic treatment within the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency and bone anti-resorptive agents etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has a history of or active interstitial lung disease, autoimmune lung disease, severe asthma requiring daily medication.
• Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with a patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• NuGenerex Immuno-Oncology: lead
• Merck Sharp & Dohme LLC: collaborator
• NSABP Foundation Inc: collaborator

Study Sites (6)

Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

Location

Crossroads Cancer Center

Effingham, Illinois, 62401, United States

Location

Cancer Care Specialists of Central Illinois-Swansea

Swansea, Illinois, 62226, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Stefanie Spielman Comprehensive Cancer Center

Columbus, Ohio, 43212, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 18, 2019
• Study Start: May 3, 2019
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2024
• Last Updated: June 2, 2021

Record last verified: 2021-05

Locations

US (6)