Pembrolizumab + Chemotherapy for Breast Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Providence Health & Services

Must be taking: Paclitaxel, Capecitabine

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

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

Compensation: Varies

Number of Visits: 15

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and tolerability of pembrolizumab, an immunotherapy drug, when combined with chemotherapy. It targets individuals with triple-negative breast cancer that is either inoperable or has metastasized. Participants will receive either pembrolizumab with paclitaxel or pembrolizumab with capecitabine. This trial suits those with measurable HER2-negative breast cancer that does not respond to estrogen or progesterone. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment.

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

Research has shown that combining pembrolizumab with chemotherapy has been tested in several studies. For the pembrolizumab and paclitaxel combination, studies found it to be generally well-tolerated. Some patients experienced side effects like tiredness or nausea, but these were manageable. In one study, adding pembrolizumab to chemotherapy improved outcomes for patients with advanced triple-negative breast cancer, indicating it is safe.

For the pembrolizumab and capecitabine combination, a study focused on safety found it was also tolerable. Some side effects like redness and swelling on the hands and feet, and diarrhea were reported, but these did not outweigh the potential benefits of the treatment.

In both combinations, pembrolizumab has shown promise in improving treatment outcomes, and its use with these chemotherapies is considered safe enough to continue exploring in trials. This suggests that while there are side effects, they are manageable and expected for cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pembrolizumab, an immunotherapy, with traditional chemotherapy drugs like paclitaxel and capecitabine. Unlike standard breast cancer treatments that mainly focus on directly attacking cancer cells, pembrolizumab works by boosting the body's immune system to better recognize and fight cancer. This unique approach potentially enhances the effectiveness of chemotherapy by helping the immune system target cancer cells more efficiently. By integrating these modes of action, the treatments aim to improve outcomes for patients with breast cancer, offering a promising new strategy beyond conventional therapies.

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

Research has shown that combining pembrolizumab with chemotherapy can benefit patients with triple-negative breast cancer. In this trial, participants in Arm A will receive pembrolizumab with weekly paclitaxel. Studies found this combination reduced the risk of cancer growth or spread by 35% compared to chemotherapy alone. Participants in Arm B will receive pembrolizumab with capecitabine, and early results suggest this combination may extend patient survival more than chemotherapy alone. These combinations show promise for treating advanced stages of this aggressive breast cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

David Page, MD

Principal Investigator

Medical Oncologist

Are You a Good Fit for This Trial?

This trial is for adults with metastatic/unresectable triple negative breast cancer who have not received certain treatments recently. Participants must be in good health, with proper organ function and performance status, and cannot be pregnant or breastfeeding. They should not have active infections or severe psychiatric issues that could affect participation.

Inclusion Criteria

Be willing and able to provide written informed consent/assent for the trial

My breast cancer is HER2-negative.

My breast cancer is not driven by estrogen or progesterone.

Exclusion Criteria

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

You are allergic to pembrolizumab or any of its ingredients.

I haven't had cancer treatment with a monoclonal antibody in the last 4 weeks, except for Denosumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pilot Phase

Patients are enrolled to one of two experimental arms: pembrolizumab + weekly paclitaxel or pembrolizumab + capecitabine

6 weeks

Weekly visits for paclitaxel or bi-weekly visits for capecitabine

Treatment

Participants receive pembrolizumab every three weeks and continue treatment until disease progression or other discontinuation criteria, up to 24 months

24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

CT or MRI scan at 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests the safety of pembrolizumab combined with chemotherapy (paclitaxel or capecitabine) for patients with a specific type of advanced breast cancer. The goal is to see how well patients tolerate this combination therapy as their first or second-line treatment.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 2 Interventions

pembrolizumab + capecitabine

Group II: Arm A Experimental Treatment 2 Interventions

pembrolizumab + weekly paclitaxel

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

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

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]

Capecitabine (Xeloda) is an oral chemotherapy that delivers 5-FU directly to tumors, offering superior response rates and equivalent survival outcomes compared to intravenous 5-FU in first-line metastatic colorectal cancer (MCRC).

Capecitabine has a favorable safety profile, with manageable side effects like hand-foot syndrome and diarrhea, allowing for prompt dose adjustments without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. Sternberg, CN., Reichardt, P., Holland, M.[2015]

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]

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, 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]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7057426/

Phase II study of pembrolizumab and capecitabine for triple ... The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with ...

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

Pembrolizumab plus Chemotherapy in Advanced Triple ... In this trial, first-line treatment with pembrolizumab–chemotherapy resulted in significantly longer overall survival than chemotherapy alone ...

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01437-1/fulltext

Adjuvant capecitabine in patients with triple-negative ... In terms of outcomes, among patients with TNBC in CREATE-X, the 5-year DFS rate was significantly higher in patients treated with capecitabine ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12414891/

Adjuvant capecitabine in patients with triple-negative ... Real-world utilization of adjuvant capecitabine and outcomes data for patients with TNBC and RD are limited. •. Among patients with TNBC with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05973864

Capecitabine Plus Pembrolizumab in Patients With Triple ... The goal of this clinical trial is to evaluate the efficacity and safety of pembrolizumab and capecitabine on the invasive disease-free survival, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05973864

Capecitabine Plus Pembrolizumab in Patients With Triple ... The goal of this clinical trial is to evaluate the efficacity and safety of pembrolizumab and capecitabine on the invasive disease-free survival, ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.1033

Safety and efficacy of pembrolizumab (pembro) plus ... We hypothesize that concurrent pembro plus standard-of-care chemotherapy is safe, and may increase clinical benefit by allowing for earlier treatment with anti ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37344474/

A phase Ib trial of pembrolizumab plus paclitaxel or flat- ... We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m 2 weekly) or flat-dose ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000390

Real-world safety and effectiveness of neoadjuvant ... Neoadjuvant chemotherapy (NAC) with the addition of pembrolizumab has become the standard of care for early-stage II-III triple-negative breast cancer (TNBC).