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

74 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug pembrolizumab in treating cancer?

Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It is approved for use in these cancers and has demonstrated safety and efficacy in clinical trials. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Mifepristone generally safe for humans?

Pembrolizumab has been studied in various cancers and is generally well tolerated, but it can cause side effects like nausea, fatigue, and rare immune-related issues such as type 1 diabetes and lung inflammation (pneumonitis). Mifepristone, known for its use in other conditions, is not specifically mentioned in these studies, so its safety in combination with Pembrolizumab is not detailed here. ^{1 2 6 7 8}

What makes the drug combination of Pembrolizumab and Mifepristone unique for breast cancer treatment?

The combination of Pembrolizumab and Mifepristone for breast cancer is unique because it pairs an immune checkpoint inhibitor (Pembrolizumab) with a progesterone receptor antagonist (Mifepristone), potentially enhancing the immune system's ability to fight cancer cells while also targeting hormone pathways, which is different from standard treatments that often focus on chemotherapy or hormone therapy alone. ^{9 10 11 12 13}

What is the purpose of this trial?

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. Patients who are deemed eligible and have signed informed consent will be treated with pembrolizumab at a fixed dose of 200 mg intravenously on day 1 of each 21 day cycle for each dose level. Mifepristone 300mg PO be administered daily starting the week prior to pembrolizumab. Once the safety of the combination is confirmed (study will be paused at least 6 weeks after first 10 patients are enrolled for safety evaluation), dose expansion cohorts will be performed in parallel for two cohorts: cohort 1 in triple-negative breast cancer and cohort 2 in hormone receptor positive breast cancer.

Research Team

Rita Nanda, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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 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]

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]

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]

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 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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Repurposing denosumab in breast cancer beyond prevention of skeletal related events: Could nonclinical data be translated into clinical practice? [2022]

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

Cancer Treatment-Induced Bone Loss: Role of Denosumab in Non-Metastatic Breast Cancer. [2022]

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

Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Severe and prolonged hypocalcemia after a single dose of denosumab for metastatic breast cancer with diffuse bone involvement without prior calcium/vitamin D supplementations. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Denosumab in breast cancer treatment. [2015]