Pembrolizumab + Cryoablation for Breast Cancer

Recruiting at 6 trial locations

Overseen By Larry Norton, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: PD-1 inhibitors

Disqualifiers: No cryoablation site, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with metastatic triple-negative breast cancer. It aims to determine whether combining pembrolizumab (an immunotherapy that helps the immune system fight cancer) with cryoablation (a procedure that freezes and destroys cancer cells) is more effective than pembrolizumab alone. Participants will be randomly assigned to receive either the drug alone or the drug with the freezing treatment. Those with breast cancer that has spread and can be treated with cryoablation might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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

The trial does not specify if you need to stop your current medications. However, it allows certain systemic therapies to be continued, so it's best to discuss your specific medications with your medical oncologist.

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

Research has shown that pembrolizumab is generally well-tolerated, even when combined with cryoablation. The FDA has approved pembrolizumab alone for other types of cancer, indicating its relative safety.

In studies where pembrolizumab was combined with cryoablation, results suggested this combination can be safe for treating breast cancer. Most side effects were mild to moderate, similar to those experienced with pembrolizumab alone, such as tiredness, fever, and mild pain at the cryoablation site.

Since this trial is in an early stage, it primarily focuses on safety, with researchers closely monitoring for any serious side effects. So far, no unexpected safety issues have emerged, suggesting this treatment might be a safe option for patients with metastatic breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and cryoablation for treating metastatic triple negative breast cancer because it brings a novel approach to this challenging condition. Unlike traditional chemotherapy, which targets rapidly dividing cells broadly, pembrolizumab is an immunotherapy that specifically helps the immune system recognize and attack cancer cells. Cryoablation adds another layer of innovation by freezing and destroying tumor tissue directly, which can potentially enhance the immune response initiated by pembrolizumab. This dual approach not only targets the cancer more precisely but also aims to provoke a stronger and more sustained immune attack on the tumors.

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

In this trial, participants will receive either pembrolizumab alone or pembrolizumab combined with cryoablation. Research has shown that combining pembrolizumab with cryoablation might help the body's immune system fight triple-negative breast cancer more effectively. Studies have found that pembrolizumab alone can greatly improve survival rates for patients with this cancer type. When used with chemotherapy, pembrolizumab lowered the risk of the cancer worsening by 35% compared to a placebo. Cryoablation, which freezes cancer cells, may further enhance these effects by helping the immune system better target the cancer. Early research suggests that this combination could be more effective than using pembrolizumab alone. ^{1 2 6 7 8}

Who Is on the Research Team?

Yolanda Bryce, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic breast cancer. Participants will be randomly assigned to receive either a combination of pembrolizumab and cryoablation or just pembrolizumab.

Inclusion Criteria

My breast cancer is triple-negative and has spread.

I am planned to receive Pembrolizumab as an initial treatment.

I have a tumor suitable for freezing treatment, as confirmed by a specialist.

Exclusion Criteria

I am not planned to receive Pembrolizumab as a standard treatment.

My doctor says I can't have PD-1 inhibitor treatment.

My condition cannot be treated with cryoablation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with cryoablation or pembrolizumab alone

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cryoablation
• Pembrolizumab

Trial Overview The study is testing the effectiveness of combining pembrolizumab, an immunotherapy drug, with cryoablation—a procedure that freezes cancer cells—compared to using pembrolizumab alone in treating metastatic breast cancer.

How Is the Trial Designed?

Group I: Pembrolizumab + Cryoablation Experimental Treatment 2 Interventions

Participants will have a diagnosis of metastatic triple negative breast cancer or locally advanced inoperable triple negative breast cancer. Participants will be randomized 2 (cryoablation arm): 1 (no cryoablation arm).

Group II: Pembrolizumab Active Control 1 Intervention

Participants will have a diagnosis of metastatic triple negative breast cancer or locally advanced inoperable triple negative breast cancer. Participants will be randomized 2 (cryoablation arm): 1 (no cryoablation arm).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

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 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 (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

A study of 112 patients with non-small cell lung cancer (NSCLC) found that EBUS TBNA is effective for obtaining samples suitable for PD-L1 testing, with 82% of samples adequate for all ancillary tests.

The results showed a high satisfaction rate for PD-L1 expression testing, with 86% of cases yielding satisfactory results and 32% of patients exhibiting high PD-L1 expression levels (>50%), which is important for treatment decisions with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. Biswas, A., Leon, ME., Drew, P., et al.[2018]

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, 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 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/NCT06246968

A Study of Pembrolizumab and Cryoablation in People ... Does Cryoablation Boost Immune Response Improving the Benefits of Pembrolizumab in Patients With Metastatic or Locally Advanced Triple Negative Breast Cancer?

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02447003

NCT02447003 | Study of Pembrolizumab (MK-3475) ... This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC).

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202809

Pembrolizumab plus Chemotherapy in Advanced Triple ... The addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01265

Pembrolizumab and Cryoablation for the Treatment of ... This phase I trial compares the safety and effectiveness of pembrolizumab plus cryoablation to pembrolizumab alone in treating patients with triple negative ...

5. keytruda.com keytruda.com/triple-negative-breast-cancer/clinical-trial-results/advanced-tnbc/

Triple-negative breast cancer (TNBC) - clinical trials KEYTRUDA + chemotherapy reduced the risk of cancer spreading, growing, or getting worse by 35% compared to placebo + chemotherapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10582696/

Leveraging cryoablation and checkpoint inhibitors for high- ... Despite recent advances in therapeutic options, select subtypes of breast cancers, such as triple-negative breast cancers (TNBC) remain at high risk for early ...

7. mskcc.org mskcc.org/cancer-care/clinical-trials/23-390

A Phase 1 Study of Pembrolizumab Immunotherapy and ... Researchers want to see if adding cryoablation to immunotherapy is better than immunotherapy alone for breast cancer.

8. withpower.com withpower.com/trial/phase-1-carcinoma-2024-28092

Pembrolizumab + Cryoablation for Breast Cancer This Phase 1 medical study run by Memorial Sloan Kettering Cancer Center is evaluating whether Pembrolizumab will have tolerable side effects & efficacy for ...