Pembrolizumab + IRX-2 + Chemotherapy for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Providence Health & Services

Must not be taking: Immunosuppressants, Steroids, Quinolones, others

Disqualifiers: Invasive malignancy, Autoimmune disease, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with triple negative breast cancer (TNBC), a type of breast cancer lacking certain receptors. It combines pembrolizumab, an immunotherapy, with chemotherapy and tests it with or without an additional immune-boosting treatment called IRX-2. Participants include those who haven't received prior treatment for their locally advanced but non-spreading TNBC and have been diagnosed with this specific cancer type. The study aims to determine how effectively these treatments work together to shrink tumors before surgery. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that pembrolizumab, when combined with chemotherapy, maintains a strong safety record. One study found that about 87% of patients receiving pembrolizumab with chemotherapy were still alive after five years, suggesting this treatment may extend patient survival. However, some patients experienced significant side effects, potentially leading to long-term health issues.

For IRX-2, studies have demonstrated its safety for patients with early-stage breast cancer. Participants in these studies tolerated IRX-2 well, with no major safety concerns reported, indicating it might be a safe option for many.

Both treatments are now undergoing testing together in a trial for triple-negative breast cancer, a more aggressive form of cancer. While pembrolizumab and IRX-2 each have their own safety records, researchers are carefully evaluating the combination to ensure it remains safe when used with chemotherapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care options for breast cancer, which often rely on chemotherapy alone, these new treatments combine pembrolizumab, an immune checkpoint inhibitor, with IRX-2, an immunomodulatory agent. This combination aims to enhance the body's immune response against cancer cells. Researchers are excited because pembrolizumab works by blocking the PD-1 pathway, which helps the immune system recognize and attack cancer cells more effectively. Moreover, the addition of IRX-2, which is derived from human peripheral blood lymphocytes, may further boost the immune response, potentially improving treatment outcomes compared to traditional chemotherapy alone.

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

Research shows that pembrolizumab, when combined with chemotherapy, yields promising results in treating various cancers, including breast cancer. For triple-negative breast cancer (TNBC), this combination has nearly doubled the rate of complete tumor disappearance before surgery. In this trial, one group will receive pembrolizumab with chemotherapy alone, while another group will receive pembrolizumab, IRX-2, and chemotherapy. Studies suggest that adding IRX-2 to this regimen can further enhance outcomes. Specifically, one study found that using IRX-2, pembrolizumab, and chemotherapy together resulted in an 83% complete response rate, meaning the cancer was undetectable after treatment. These treatments enhance the immune system's ability to fight cancer. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with untreated, non-metastatic triple negative breast cancer (TNBC) who have good performance status and organ function. Participants must not be pregnant, agree to use contraception, and provide a tumor biopsy. Exclusions include recent live vaccines, other cancers within 5 years, past year chemotherapy or radiation therapy, active autoimmune diseases requiring treatment in the last 2 years, HIV or Hepatitis B/C infection.

Inclusion Criteria

Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.

My breast cancer is triple-negative, confirmed by local testing.

Your heart's pumping function is normal, as shown by a recent heart scan.

Exclusion Criteria

I've had chemotherapy, targeted therapy, and radiation in the last year.

Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.

I have been treated with specific immune therapy or participated in MK-3475 trials.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Pembrolizumab induction (single-dose 200mg IV), with or without IRX-2 and cyclophosphamide

3 weeks

Chemotherapy

Pembrolizumab Q3W + paclitaxel weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide Q3W x 4 cycles

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• IRX-2
• Pembrolizumab

Trial Overview The study tests pembrolizumab combined with chemotherapy and different immunotherapy induction regimens as pre-surgery treatment for TNBC. It's an open-label Phase II trial where patients are openly assigned to treatments to assess clinical response and immune system activity.

How Is the Trial Designed?

Group I: Control Experimental Treatment 1 Intervention

Control Arm: (Pembro + ACT): Pembrolizumab induction (single-dose 200mg IV), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery.

Group II: Arm A Experimental Treatment 2 Interventions

• Arm A: (Pembro + IRX-2 + ACT): Pembrolizumab (single-dose 200mg IV) + cyclophosphamide (single-dose 300 mg/m2 IV) + IRX-2 induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by IRX-2 re-induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery.

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?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Brooklyn ImmunoTherapeutics, LLC

Industry Sponsor

Trials

8

Recruited

5,500+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

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 real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

The PELICAN-IPC trial is investigating the safety and efficacy of pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with HER2-negative inflammatory breast cancer (IBC), which is known for its aggressive nature and poor treatment outcomes.

The primary goal of the trial is to assess the rate of pathologic complete response (pCR) after treatment, while also monitoring safety and tolerability, with additional objectives focusing on long-term survival outcomes and translational research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. Bertucci, A., Bertucci, F., Zemmour, C., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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 long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

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]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., 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]

Citations

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NeoIRX trial: Immunologic induction with peri-lymphatic ... The IRX-2 arm achieved 83% pCR (n = 5/6, CI 36-100%) compared to 33% pCR with pembro alone (n = 2/6, CI 4-78%). The regimen was well-tolerated ...

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A Phase Ib Study of Preoperative, Locoregional IRX-2 ... Conclusions: IRX-2 is safe in early-stage breast cancer. Potentially favorable immunomodulatory changes were observed, supporting further study of IRX-2 in ...

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Phase Ib trial of IRX-2 plus durvalumab in patients with ... Median overall survival and progression-free survival (PFS) were 6.18 months (95 % CI, 2.66–8.61) and 2.53 months (95 % CI, 1.81–4.04), respectively. One ...