This phase II trial studies the side effects and best dose of ivermectin in combination with balstilimab or pembrolizumab and to see how well they they work in shrinking tumors in patients with triple negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as balstilimab or pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivermectin may help block the formation of growths that may become cancer. Giving ivermectin with balstilimab or pembrolizumab may increase the effect of balstilimab or pembrolizumab in shrinking tumors in patients with triple negative breast cancer. The secondary objectives of the study include evaluating the following efficacy outcomes: objective response rate (ORR), progression free survival (PFS), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), and patients' quality of life (QOL) by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
Patients receive ivermectin orally (PO) once daily (QD) on days 1-3, 8-10, and 15-17. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive balstilimab or pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 90 days and then periodically thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Ivermectin at the assigned dose administered PO on Days 1-3, 8-10, 15-17 of each 21 day cycle (Days1-3 of each week).
Balstilimab 300 mg administered intravenously on Day 1 of each 21 day cycle.
Pembrolizumab 200 mg IV on Day 1 of each 21 day cycle
Cedars-Sinai Medical Center
Los Angeles, California, United States
RECRUITINGIncidence of adverse events
Phase 1: To determine the recommended phase 2 dose of ivermectin in combination with balstilimab or pembrolizumab using NCI-CTCAE v5.0
Time frame: From start of study treatment until 90 days after treatment completion
Objective response rate
Phase 2: To determine the efficacy of ivermectin in combination with balstilimab or pembrolizumab in mTNBC using the objective response rate (ORR)
Time frame: From start of study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 2 years.
Objective response rate
Evaluate the efficacy of ivermectin in combination with balstilimab or pembrolizumab in mTNBC using objective response rate (ORR) using RECIST 1.1
Time frame: From start of study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 2 years.
Progression free survival
From start of therapy until first documentation of disease progression per RECIST 1.1 or death due to any cause.
Time frame: From start of study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 6 years.
Overall survival
From start of study treatment to date of death due to any cause. Patient's last known to be alive are censored at date of last contact.
Time frame: From start of study treatment to death or last contact. Assessed up to 6 years
Duration of response
Measured from the date of first objective response recorded (CR or PR) until progression per RECIST 1.1, death or last contact (censored). Patient's last known to be alive are censored at date of last contact.
Time frame: From the date of first objective response recorded until disease progression, death or last contact. Assessed up to 6 years
Clinical benefit rate
Defined as progression-free for at least 6 months or CR or PR per RECIST 1.1.
Time frame: From start of study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 6 years.
Patients' quality of life
Evaluated by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 per standardized EORTC scoring guidelines.
Time frame: On day 1 of each 3 week cycle and at end of treatment visit. Assessed up to 2 years.
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