Ivermectin + Balstilimab for Breast Cancer

Recruiting at 1 trial location

Overseen By Clinical Trial Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Warfarin, Live vaccines

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining ivermectin with either balstilimab or pembrolizumab in shrinking tumors in patients with metastatic triple-negative breast cancer. Balstilimab (also known as AGEN1884) and pembrolizumab are immunotherapy drugs that help the immune system attack cancer, while ivermectin may prevent new tumor growth. The trial seeks to determine the optimal dose and identify any side effects. It is suitable for individuals whose cancer has progressed after 1-2 previous treatments. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent or if you are taking warfarin. Other medications like low molecular weight heparin or factor Xa inhibitors are allowed. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like chemotherapy, radiation, and immunotherapy are not allowed within specific time frames before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that ivermectin is generally safe for humans and is already used to treat certain parasitic infections. Early research suggests that when combined with balstilimab, most patients tolerate the treatment without major issues. Some may experience mild side effects, such as nausea or tiredness, but serious reactions are rare. The trials aim to determine the optimal dose to minimize side effects while effectively treating cancer. Since both drugs have undergone previous testing, there is some confidence in their safety for this new use in breast cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Ivermectin and Balstilimab for breast cancer treatment because these drugs offer a unique approach compared to standard treatments like chemotherapy and hormone therapy. Balstilimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, which is different from traditional treatments that directly target the cancer cells themselves. Meanwhile, Ivermectin, typically known as an antiparasitic drug, is being repurposed for its potential anticancer properties, adding a fresh avenue for tackling breast cancer. This combination aims to enhance the body's natural defenses against cancer while potentially offering a new, effective option for patients.

What evidence suggests that this trial's treatments could be effective for metastatic triple negative breast cancer?

Research suggests that ivermectin might help the immune system fight cancer more effectively by causing cancer cells to die in a way that attracts immune cells to the tumor. In this trial, participants will receive a combination of ivermectin and balstilimab. Studies have shown that ivermectin shows promise when used with drugs like balstilimab, which enhance the immune system's attack on cancer cells. Balstilimab, an immune therapy, has been tested with some success in other types of cancer. Together, ivermectin and balstilimab might help shrink tumors in triple-negative breast cancer, a difficult type to treat. Early results are promising, but more research is needed to confirm their effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Yuan Yuan, MD PhD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic triple negative breast cancer who have tried 1-2 systemic therapies. They must be in good health otherwise, with a life expectancy of over 3 months and an ECOG score of ≤1. Women must not be pregnant or breastfeeding and agree to contraception. People can't join if they've had certain heart problems, severe lung conditions, active infections like Hepatitis B/C or HIV, autoimmune diseases requiring recent treatment, brain metastases unless stable without steroids for 14 days, or are on other clinical trials.

Inclusion Criteria

I have recovered from side effects of cancer treatment, except for hair loss.

You are expected to live for more than 3 months.

My cancer is PD-L1 negative for the Phase 2 trial.

Exclusion Criteria

I have an active tuberculosis infection.

I don't have active brain metastases and haven't needed steroids for them in the last 14 days.

I have a history of Hepatitis B or active Hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ivermectin orally on days 1-3, 8-10, and 15-17, and balstilimab or pembrolizumab intravenously on day 1 of each 21-day cycle, for up to 35 cycles or 2 years

Up to 2 years

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

90 days

Periodic visits

Long-term follow-up

Participants are periodically monitored for overall survival and progression-free survival

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Ivermectin

Trial Overview The trial is testing the combination of Ivermectin and Balstilimab to see how well it works in shrinking tumors in patients with advanced breast cancer. It's a phase II study which means they're looking at effectiveness and determining the best dose while monitoring side effects closely.

How Is the Trial Designed?

Group I: Treatment (ivermectin, balstilimab) Experimental Treatment 3 Interventions

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

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Yuan Yuan

Lead Sponsor

Trials

2

Recruited

30+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Agenus Inc.

Industry Sponsor

Trials

58

Recruited

4,900+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Published Research Related to This Trial

In the PALOMA-3 trial, Korean patients with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer treated with palbociclib plus fulvestrant experienced a significantly longer median progression-free survival (PFS) of 12.3 months compared to 5.4 months for those on placebo plus fulvestrant.

Palbociclib was generally safe, with neutropenia being the most common side effect, and it showed a confirmed objective response rate of 21.1% compared to 11.8% for the placebo group, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Plus Fulvestrant in Korean Patients from PALOMA-3 With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Kim, JH., Im, SA., Sim, SH., et al.[2021]

Nivolumab combined with ipilimumab demonstrated significantly better overall survival compared to BRAF + MEK inhibitors, with hazard ratios indicating a 36% to 44% reduction in the risk of death after 12 months.

While nivolumab + ipilimumab had improved survival outcomes, it also resulted in a higher rate of grade 3/4 adverse events (54.1%) compared to dabrafenib + trametinib (31.6%) and similar rates to vemurafenib + cobimetinib (59.5%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison. Atkins, MB., Tarhini, A., Rael, M., et al.[2020]

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

In a phase II trial involving 161 women with recurrent or metastatic cervical cancer, balstilimab, an anti-PD-1 antibody, showed an objective response rate (ORR) of 15%, indicating it can provide meaningful antitumor activity in this patient population.

The treatment was generally safe, with manageable side effects; the most common severe adverse events were immune-mediated enterocolitis (3.1%) and diarrhea (1.9%), suggesting that balstilimab has a favorable safety profile for patients who have previously undergone platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. O'Malley, DM., Oaknin, A., Monk, BJ., et al.[2022]

In a study of 396 female patients with hormone receptor positive, HER2-negative metastatic breast cancer receiving CDK4 and 6 inhibitors, the most common adverse events were neutropenia, diarrhea, and fatigue, with varying frequencies depending on the specific drug used.

The study found that while the overall incidence of adverse events was lower than in clinical trials, the rates of dose reductions and treatment holds due to these events were higher, suggesting that clinicians may be actively managing side effects to help patients continue their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. Price, GL., Sudharshan, L., Ryan, P., et al.[2022]

The combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib significantly improved progression-free survival in patients with BRAF V600 mutation-positive melanoma, with a median of 9.9 months compared to 6.2 months for those receiving vemurafenib alone.

Patients receiving the combination therapy also had a higher response rate, with 68% showing complete or partial responses compared to 45% in the control group, although this came with a slight increase in severe adverse events (65% vs. 59%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. Larkin, J., Ascierto, PA., Dréno, B., et al.[2022]

In a randomized phase 2 trial involving 92 patients with metastatic melanoma, the combination of ipilimumab (CTLA-4 blockade) and nivolumab (PD-1 blockade) significantly improved progression-free survival compared to ipilimumab alone, with a hazard ratio of 0.63.

The combination therapy also showed a higher objective response rate of 28% compared to 9% for ipilimumab alone, although it was associated with increased treatment-related adverse events (57% vs. 35% for ipilimumab alone), consistent with known toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial. VanderWalde, A., Bellasea, SL., Kendra, KL., et al.[2023]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

A comprehensive analysis of 16 clinical trials with 5976 participants shows that combined BRAF and MEK inhibition significantly prolongs progression-free survival (PFS) and overall survival (OS) in metastatic melanoma compared to single-agent therapies.

The combination therapy also results in a higher objective response rate (ORR), indicating that targeting both BRAF and MEK simultaneously is a more effective treatment strategy for patients with metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials. Mai, R., Zhou, S., Zhong, W., et al.[2018]

A network meta-analysis of three phase-3 trials involving 1230 patients found that the combinations of BRAF and MEK inhibitors (dabrafenib plus trametinib, vemurafenib plus cobimetinib, and encorafenib plus binimetinib) showed similar efficacy in terms of overall survival, progression-free survival, and overall response rate for treating advanced BRAF V600 mutated malignant melanoma.

While the efficacy of these drug combinations was comparable, the safety profiles varied slightly, indicating that specific molecular properties of each drug combination may influence the types and rates of side effects experienced by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma. Consoli, F., Bersanelli, M., Perego, G., et al.[2022]

CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) significantly improve progression-free survival in patients with hormone receptor-positive HER2-negative metastatic breast cancer when used alongside endocrine therapy, with a consistent hazard ratio of around 0.5 across phase III trials.

These treatments are generally well tolerated, with manageable side effects; however, abemaciclib is associated with a higher incidence of diarrhea, while palbociclib and ribociclib are more likely to cause hematological toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. Eggersmann, TK., Degenhardt, T., Gluz, O., et al.[2019]

In a phase Ib study involving 26 patients with metastatic ER+ breast cancer, the combination of alpelisib and letrozole was found to be safe, with a maximum-tolerated dose of 300 mg/d and manageable side effects like hyperglycemia and fatigue.

The treatment showed a clinical benefit rate of 35%, particularly benefiting patients with PIK3CA mutations, where 44% experienced a lack of disease progression for at least 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer. Mayer, IA., Abramson, VG., Formisano, L., et al.[2022]

A review of 11,721 serious adverse event reports from patients treated with BRAF and MEK inhibitors revealed that different combinations have unique safety profiles, with V+C showing a high incidence of skin toxicities like Stevens-Johnson syndrome.

The combination E+B was notably associated with an increased risk of peripheral neuropathies and renal disorders, as well as a significant rise in reports of Guillain-Barré syndrome, indicating that while these treatments improve survival in melanoma, they also carry serious risks that need careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of BRAF+MEK Inhibitor Combinations: Severe Adverse Event Evaluation. Meirson, T., Asher, N., Bomze, D., et al.[2020]

Citations

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A phase I/II study evaluating the safety and efficacy of ... The current phase I/II trial is designed to test the safety and efficacy of the combination of ivermectin and balstilimab in patients with mTNBC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05318469

Study Details | NCT05318469 | Ivermectin in Combination ... Giving ivermectin with balstilimab or pembrolizumab may increase the effect of balstilimab or pembrolizumab in shrinking tumors in patients with triple negative ...

3. investor.agenusbio.com investor.agenusbio.com/news/news-details/2025/Agenus-BOTBAL-Neoadjuvant-Pan-Cancer-Data-from-the-NEOASIS-Study-Presented-in-an-Oral-Session-at-AACR/default.aspx

Agenus' BOT/BAL Neoadjuvant Pan-Cancer Data from the ... This represents the third clinical study evaluating botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting, with outcomes reported in ...

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Dr Schlechter on Updated Data for Botensilimab Plus ... Benjamin L. Schlechter, MD, discusses efficayc and safety of botensilimab in combination with the anti–PD-1 antibody balstilimab in mCRC.

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Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is ... Botensilimab Effectively Treats Multiple Human Cancers. We have previously reported clinical results from an ongoing expanded phase I trial ( ...

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Ivermectin and gynecologic cancer: What's the data? - PMC A Phase I/Ii Study Evaluating the Safety and Efficacy of Ivermectin in Combination with Balstilimab in Patients with Metastatic Triple Negative ...

7. oncodaily.com oncodaily.com/oncolibrary/ivermectin-and-immunotherapy

Antiparasitic Drug Ivermectin and Immunotherapy for ... Because ivermectin has an established safety profile, is inexpensive, and is widely available, researchers have explored whether it can be “ ...

8. trialx.com trialx.com/clinical-trials/listings/236629/ivermectin-in-combination-with-balstilimab-or-pembrolizumab-in-patients-with-metastatic-triple-negative-breast-cancer/

Ivermectin in Combination With Balstilimab or ... Giving ivermectin with balstilimab or pembrolizumab may increase the effect of balstilimab or pembrolizumab in shrinking tumors in patients with ...