Pembrolizumab + Mifepristone for Breast Cancer

Overseen By Cancer Intake

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Active CNS metastases, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Until disease progression or withdrawal

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, pembrolizumab (an immunotherapy drug) and mifepristone (a hormone receptor modulator), to evaluate their effectiveness in treating advanced breast cancer. It targets two types of breast cancer: triple-negative and hormone receptor-positive. Suitable candidates for this study have breast cancer that has spread or cannot be surgically removed, and they must have tumors measurable by scan or exam. The trial will begin by confirming the combination's safety before expanding to more participants. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it mentions that mifepristone can interact with certain drugs, especially those metabolized by CYP3A4 and CYP2C9/CYP2C8 enzymes. It's important to discuss your current medications with the trial team to ensure safety.

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

Research shows that the combination of pembrolizumab and mifepristone is generally well-tolerated in patients with advanced breast cancer. Earlier studies reported some side effects, mostly mild to moderate. Common side effects included fatigue, nausea, and changes in appetite.

Pembrolizumab, also known as Keytruda, has FDA approval for treating certain types of breast cancer, indicating its safety is well-studied. However, it can cause serious side effects, such as the immune system attacking healthy organs.

Mifepristone is typically used for other conditions, but when combined with pembrolizumab, it has demonstrated a manageable safety profile. Patients should discuss potential risks and benefits with their healthcare team before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and mifepristone for advanced breast cancer because of its unique approach to treatment. Unlike standard chemotherapy or hormone therapy, pembrolizumab is an immunotherapy that boosts the body's immune system to fight cancer cells. Mifepristone, typically known for its role in reproductive health, is being explored here for its potential to block hormone receptors that help cancer grow, especially in hormone-resistant cases. This dual-action strategy not only targets the cancer cells but also aims to overcome resistance, offering new hope for patients with difficult-to-treat forms of breast cancer.

What evidence suggests that pembrolizumab plus mifepristone could be an effective treatment for advanced breast cancer?

Research has shown that combining pembrolizumab with chemotherapy extends the lives of patients with triple-negative breast cancer. This combination already has approval for patients with high-risk, early-stage cancer. In this trial, all participants will receive pembrolizumab and mifepristone. Mifepristone blocks certain hormones and might enhance the immune system's ability to fight cancer. Studies on the combination of pembrolizumab and mifepristone have demonstrated safety and efficacy in treating HER2-negative breast cancer. Early results suggest this combination could be effective for advanced breast cancer, particularly in hormone receptor-positive and triple-negative types. ^{1 2 3 4 5}

Who Is on the Research Team?

Rita Nanda, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2-negative breast cancer, including those with triple-negative or hormone receptor positive subtypes. Participants must have measurable disease and be in good health otherwise, with normal organ and marrow function. Women should not be pregnant and must use contraception; men also need to agree to use contraception. Patients can't join if they've had certain recent treatments, have specific infections or autoimmune diseases, are on conflicting medications, or have untreated brain metastases.

Inclusion Criteria

I am fully active or can carry out light work.

I am a male and will use protection or abstain from sex with women who can get pregnant during and 6 months after the study.

Patients must consent to pre and on treatment research biopsies.

Exclusion Criteria

Uncontrolled intercurrent medical or psychiatric illness that would limit compliance with study requirements.

You have had allergic reactions to drugs that are similar to pembrolizumab or mifepristone.

I am not HIV-positive or not on antiretroviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial safety evaluation with 10 patients receiving pembrolizumab and mifepristone

6 weeks

1 visit every 21 days

Treatment

Participants receive pembrolizumab every 21 days and daily mifepristone, with dose expansion cohorts for different breast cancer subtypes

Until disease progression or withdrawal

Evaluation every 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Mifepristone
• Pembrolizumab

Trial Overview The study tests Pembrolizumab combined with Mifepristone in patients who haven't responded well to other therapies. It starts with a safety check on the first ten patients using Pembrolizumab every three weeks and daily Mifepristone starting one week before that. If safe, more patients will join either of two groups based on their cancer type.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Enrollment will be paused after the first 10 patients are enrolled in the study for a safety evaluation. Once safety is confirmed, patients with triple-negative advanced breast cancer will be enrolled in cohort 2. Regardless of cohort, all eligible patients will be treated with pembrolizumab (on day 1 of every 21 day cycle), and mifepristone (administered daily starting the week prior to pembrolizumab).

Group II: Cohort 1 Experimental Treatment 2 Interventions

Enrollment will be paused after the first 10 patients are enrolled in the study for a safety evaluation. Once safety is confirmed, patients with hormone receptor positive, hormone refractory advanced breast cancer will be enrolled in cohort 1. Regardless of cohort, all eligible patients will be treated with pembrolizumab (on day 1 of every 21 day cycle), and mifepristone (administered daily starting the week prior to pembrolizumab).

Mifepristone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Mifeprex for:

• Abortion
• Cushing's Syndrome

Approved in European Union as Mifegyne for:

• Abortion
• Cushing's Syndrome

Approved in Canada as Mifeprex for:

• Abortion
• Cushing's Syndrome

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

In a phase I study involving 113 patients with advanced solid tumors, MK-4166 was found to be tolerable, with only 8% of patients experiencing treatment-related grade ≥3 adverse events and no treatment-related deaths reported.

The combination of MK-4166 with pembrolizumab showed promising efficacy, particularly in patients with immune checkpoint inhibitor (ICI)-naïve melanoma, achieving an objective response rate of 62%, indicating potential for effective treatment in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Papadopoulos, KP., Autio, K., Golan, T., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a large phase III study, denosumab significantly delayed the time to the first skeletal-related event in patients with breast cancer bone metastases compared to zoledronic acid, highlighting its efficacy as a targeted bone therapy.

Denosumab also increased bone mineral density in patients receiving aromatase inhibitors, suggesting additional benefits in the adjuvant setting beyond just managing metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab in breast cancer treatment. Drooger, JC., van der Padt, A., Sleijfer, S., et al.[2015]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In a study of 25 patients with advanced ER+/HER2- breast cancer, pembrolizumab showed a modest overall response rate of 12% and a clinical benefit rate of 20%, indicating some effectiveness in this difficult-to-treat population.

The treatment was well tolerated, with 64% of patients experiencing treatment-related adverse events, primarily mild nausea and fatigue, and no treatment-related discontinuations or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Rugo, HS., Delord, JP., Im, SA., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03225547

NCT03225547 | Study of Pembrolizumab and Mifepristone ... This is a Phase II study of pembrolizumab plus mifepristone in advanced breast cancer patients. The study will include a safety lead in of ten patients.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.1095

Phase II study of pembrolizumab plus mifepristone in ... We present the safety and efficacy of the combination of pembrolizumab and mifepristone in advanced HER2-negative breast cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39282906/

Overall Survival with Pembrolizumab in Early-Stage Triple ... Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with ...

4. merck.com merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-high-risk-early-stage-triple-negative-breast-cancer-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued/

FDA Approves KEYTRUDA® (pembrolizumab) for ... This KEYTRUDA Combination Is the First Immunotherapy Regimen Approved for High-Risk Early-Stage Triple-Negative Breast Cancer (TNBC).

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer

FDA approves pembrolizumab for high-risk early-stage ... FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. ... The main efficacy outcome measures were pathological ...