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

Trial Summary

What is the purpose of this trial?

This trial uses ivermectin and balstilimab to treat metastatic triple negative breast cancer. Ivermectin might stop new cancer growths, and balstilimab helps the immune system attack cancer cells. The goal is to shrink tumors and improve patient outcomes.

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.

What data supports the idea that Ivermectin + Balstilimab for Breast Cancer is an effective treatment?

The available research does not provide any data on the effectiveness of Ivermectin + Balstilimab for Breast Cancer. Instead, the studies focus on treatments for melanoma, a different type of cancer. Therefore, there is no evidence from the provided information to support the effectiveness of Ivermectin + Balstilimab for Breast Cancer. ^{1 2 3 4 5}

What safety data exists for Ivermectin and Balstilimab in breast cancer treatment?

The provided research does not contain specific safety data for the combination of Ivermectin and Balstilimab in breast cancer treatment. The studies mentioned focus on Balstilimab in cervical cancer and other unrelated treatments in breast cancer. Therefore, no direct safety data for this combination in breast cancer is available from the provided research. ^{6 7 8 9 10}

Is the combination of Ivermectin and Balstilimab safe for humans?

Balstilimab has been studied for safety in patients with cervical cancer, and while specific safety data for the combination with Ivermectin in breast cancer is not available, Balstilimab alone has been evaluated in humans. ^{6 7 8 9 10}

Is the drug Balstilimab, Ivermectin a promising treatment for breast cancer?

The information provided does not include any specific research or evidence about the effectiveness of Balstilimab, Ivermectin for breast cancer. Therefore, we cannot determine if it is a promising treatment based on the given data. ^{10 11 12 13 14}

How does the drug Ivermectin + Balstilimab differ from other breast cancer treatments?

Ivermectin + Balstilimab is unique because it combines an anti-parasitic drug (Ivermectin) with an immune checkpoint inhibitor (Balstilimab), which is different from the commonly used CDK4/6 inhibitors like palbociclib that target specific proteins involved in cell division. This combination may offer a novel approach by potentially enhancing the immune system's ability to fight cancer cells, unlike traditional hormone or targeted therapies. ^{10 11 12 13 14}

Research Team

Yuan Yuan, MD PhD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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 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]

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]

References

1. England 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. [2020]

2. United States 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. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. [2022]

4. United States 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. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma. [2022]

6. United States 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. [2022]

7. Korea (South) 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. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of BRAF+MEK Inhibitor Combinations: Severe Adverse Event Evaluation. [2020]

9. England 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. [2022]

10. France pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

12. New Zealand pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. [2019]

13. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer. [2022]