Ivermectin in Combination With Balstilimab or Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer

NCT05318469 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IIT2022-07-YUAN-IB-TNBC
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Metastatic Triple-Negative Breast Carcinoma; Anatomic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Incidence 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

  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)

  From start of study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 2 years.

Secondary Outcomes (6)

• Objective response rate

  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 study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 6 years.

• Overall survival

  From start of study treatment to death or last contact. Assessed up to 6 years

• Duration of response

  From the date of first objective response recorded until disease progression, death or last contact. Assessed up to 6 years

• Clinical benefit rate

  From start of study treatment until disease progression, intolerable toxicities, or withdrawal of consent. Assessed up to 6 years.

Study Arms (1)

Treatment (ivermectin, balstilimab)

EXPERIMENTAL

Patients will receive balstilimab 450 mg or pembrolizumab 200 mg, IV, on Day 1 of each 3 week cycle and ivermectin at the assigned dose (see Section 5.1, Table 5.1.2), PO, Days 1-3, 8-10, 15-17 of each cycle (Days 1-3 of each week) until disease progression, intolerable toxicities, withdrawal of consent, or up to 35 treatments or 2 years of balstilimab or pembrolizumab, whichever comes first

Drug: Ivermectin; Drug: Balstilmab; Drug: Pembrolizumab

Interventions

Ivermectin DRUG

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).

Also known as: Sklice, Stromectol

Treatment (ivermectin, balstilimab)

Balstilmab DRUG

Balstilimab 300 mg administered intravenously on Day 1 of each 21 day cycle.

Treatment (ivermectin, balstilimab)

Pembrolizumab DRUG

Pembrolizumab 200 mg IV on Day 1 of each 21 day cycle

Treatment (ivermectin, balstilimab)

Eligibility Criteria

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

You may qualify if:

• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Life expectancy \> 3 months
• Histologically confirmed metastatic triple negative breast cancer. Triple negative status will be defined as estrogen receptor (ER) and progesterone receptor (PR) ≤ 10% and HER2 negative (by immunohistochemistry \[IHC\] or fluorescence in situ hybridization \[FISH\]), per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
• Patients must have progressed on 1-2 prior lines of systemic therapy (chemotherapy and/or drug-antibody conjugate) in the metastatic setting
• Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 2 from prior anti-cancer therapy
• For Phase 2 expansion only, must be PD-L1 negative. Note: For Phase 1 safety cohort, any PD-L1 status will be allowed to enroll.
• Patients must have adequate organ function as defined in the following:
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
• Platelets ≥ 100,000/mm\^3
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN
• Aspartate aminotransferase (AST) ≤ 1.5 x ULN or ≤ 3 x ULN with liver metastases
• Alanine aminotransferase (ALT) ≤ 1.5 x ULN or ≤ 3 x ULN with liver metastases

You may not qualify if:

• 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
• Prohibited Treatments and/or Therapies:
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 28 days prior to day 1 of protocol therapy
• Prior immune checkpoint inhibitor therapy in metastatic setting (Note: Prior use of immune checkpoint inhibitor in neoadjuvant or adjuvant setting only permitted if last dose is at least 1 year from start of study intervention)
• Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
• Any 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
• Participants on any dose of warfarin. Use of low molecular weight heparin, antithrombin agents, anti-platelet agents or factor Xa inhibitors is allowed
• Participants may not be currently participating in or participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
• Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting during screening)
• Women who are or are planning to become pregnant or breastfeed
• Known allergy to any of the components within the study agents and/or their excipients
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years
• Participants must not have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Active infection requiring systemic therapy

Sponsors & Collaborators

• Yuan Yuan: lead
• Agenus Inc.: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Ivermectin; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Yuan Yuan, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Navigator

CONTACT

3104232133; GroupCancerTrialInformation@cshs.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 INVESTIGATOR
• PI Title: Medical Director, Breast Oncology DRG

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 8, 2022
• Study Start: October 13, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)