Pembrolizumab + Chemotherapy for Breast Cancer

Overseen By Oluchi Oke, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Stage 2-4 cancer, 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: Unknown

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—pembrolizumab (an immunotherapy drug), carboplatin, and paclitaxel—to evaluate their effectiveness in treating early-stage Triple Negative Breast Cancer (TNBC). Researchers aim to determine if this combination can effectively eliminate cancer cells before and after surgery. If cancer becomes undetectable after the initial treatment, participants will receive pembrolizumab alone for up to 13 cycles. Those with detectable cancer will receive additional drugs, doxorubicin and cyclophosphamide, alongside pembrolizumab. Individuals with Stage 1 TNBC, diagnosed with tumors that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic steroids or have received recent cancer therapies, you may need to adjust or stop those before joining the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that the treatments under study—carboplatin, paclitaxel, and pembrolizumab—have different safety profiles.

Carboplatin, like most chemotherapy drugs, can cause side effects. It may lower blood cell counts, increasing susceptibility to infections or bleeding. However, previous studies suggest it is generally well-tolerated for treating breast cancer.

Paclitaxel can also lower white blood cell counts, raising the risk of infection. Some patients might experience allergic reactions, but these are usually manageable.

Pembrolizumab, an immune-based therapy, can sometimes cause the immune system to attack the body's own organs, leading to serious reactions. These immune responses can affect different body systems, but they don't occur in everyone and can often be treated effectively.

These treatments have been tested in various settings and are generally considered safe for clinical trials. However, discussing potential risks with a healthcare provider is important for those considering 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 with chemotherapy for breast cancer because it leverages the immune system in a unique way. Pembrolizumab is an immunotherapy drug that works by blocking the PD-1 pathway, helping the immune system recognize and attack cancer cells more effectively. This approach is different from standard treatments like surgery, radiation, or traditional chemotherapy alone, which don't specifically harness the body's immune response. By combining pembrolizumab with chemotherapy drugs like carboplatin and paclitaxel, this treatment aims to enhance the efficacy of chemotherapy while potentially reducing cancer recurrence. This novel strategy could offer more comprehensive care by integrating the body's natural defenses with conventional cancer-fighting methods.

What evidence suggests that this trial's treatments could be effective for Triple Negative Breast Cancer?

Research has shown that adding carboplatin to chemotherapy can improve outcomes for people with early-stage triple-negative breast cancer (TNBC). Studies indicate that carboplatin enhances treatment effectiveness and can extend patient survival. Paclitaxel, another chemotherapy drug, works well against breast cancer, especially when combined with other treatments. In this trial, participants will receive a combination of carboplatin, paclitaxel, and pembrolizumab. Pembrolizumab, an immunotherapy drug, has been shown to extend survival when combined with chemotherapy in advanced TNBC. This trial aims to increase the chance of a complete response, meaning no visible cancer remains, by using these treatments together. ^{2 6 7 8 9}

Who Is on the Research Team?

Oluchi Oke, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage Triple Negative Breast Cancer (stage 1, tumors between 1-3 cm, no spread to lymph nodes or other body parts). Participants should not have had previous breast cancer treatment.

Inclusion Criteria

Hepatitis B and C positive participants must meet specific criteria for eligibility

Participant must provide written informed consent

My breast cancer is early stage, not spread to lymph nodes or other parts.

Exclusion Criteria

Pregnancy, breastfeeding, or planning to conceive during study period

I haven't had cancer treatment in the last 4 weeks.

I am on treatment for an infection that has lasted more than 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 4 cycles of Pembrolizumab, Carboplatin, and Paclitaxel

12 weeks

Pathologic Complete Response

Participants with a pathological complete response receive up to 13 cycles of pembrolizumab alone

Approximately 39 weeks

Non-Pathologic Complete Response

Participants without a pathological complete response receive 4 cycles of pembrolizumab with doxorubicin and cyclophosphamide, followed by 9 cycles of pembrolizumab alone

Approximately 39 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests the effectiveness of combining pembrolizumab (an immunotherapy drug) with carboplatin and paclitaxel (chemotherapy drugs) before surgery in patients with specific early-stage breast cancer.

How Is the Trial Designed?

Group I: Pathologic Complete Response Experimental Treatment 3 Interventions

If a participant's tissue shows a pathological complete response to treatment, participants will receive up to 13 cycles of pembrolizumab alone. Pathological complete response means that the study team cannot find any evidence of cancer in the breast or lymph node tissue sample that was removed during the participants surgery, after the participant completes the 4 cycles of carboplatin, pembrolizumab and paclitaxel.

Group II: Non-Pathologic Complete Response Experimental Treatment 5 Interventions

If a participant's tissue does not show a pathological complete response, the participant will receive 4 cycles of pembrolizumab plus 2 other drugs (doxorubicin and cyclophosphamide), followed by 9 cycles of pembrolizumab alone.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

In a phase 1 study involving Japanese patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy demonstrated a feasible safety profile, with only one dose-limiting toxicity reported in part B and two in part C, indicating that this treatment can be safely administered.

The overall response rates were promising, with 73% in the nonsquamous group and 50% in the squamous group, showing significant antitumor activity regardless of PD-L1 status, which aligns with findings from international trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. Kurata, T., Nakagawa, K., Satouchi, M., et al.[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 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]

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 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]

In a study of 364 patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy, the median time on treatment was 6.5 months, indicating a substantial duration of therapy in a real-world setting.

The median overall survival for these patients was 15.3 months, which aligns closely with results from clinical trials, demonstrating the efficacy of pembrolizumab-chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Pembrolizumab Plus Chemotherapy for Advanced Squamous NSCLC: Real-World Outcomes at U.S. Oncology Practices. Liu, SV., Rai, P., Wang, D., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11688104/

First-line carboplatin-based chemotherapy may be ... However, the results showed that carboplatin-based regimens had good efficacy and safety in HER2-low advanced breast cancer. Secondly, as of the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35462344/

An individual participant data and trial-level Meta-analysis Results: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I2 45%, p < 0.001) compared with AT at trial ...

3. breastcancer.org breastcancer.org/research-news/adding-carboplatin-to-chemotherapy-before-surgery-improves-early-stage-triple-negative-breast-cancer-outcomes

Adding Carboplatin to Chemotherapy Before Surgery ... Adding Carboplatin to Chemotherapy Before Surgery Improves Early-Stage Triple-Negative Breast Cancer Outcomes ... This study's results ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01023

Addition of Carboplatin to Sequential Taxane ... Carboplatin did not significantly increase EFS but significantly increased the OS in patients with TNBC, with benefits confined to premenopausal ...

5. cancernetwork.com cancernetwork.com/view/carboplatintp-more-effective-tp-her-2-breast-cancer

Carboplatin/TP More Effective Than TP in HER-2+ Breast ... In that trial, the TP combination produced a response rate of 41% vs 17% for pac-litaxel alone. Time to progression increased from 3.0 months on the single- ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/020452s005lbl.pdf

PARAPLATIN Label CLINICAL PHARMACOLOGY. Carboplatin, like cisplatin, produces predominantly interstrand DNA cross-links rather than DNA-protein cross-links.

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00018-7/pdf

Long-term efficacy and safety of addition of carboplatin with ... In the BrighTNess study, second malignancies were reported as AESIs, but were also to be identified as an EFS event in the absence of disease.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02531932

NCT02531932 | Comparison of Single-Agent Carboplatin ... The purpose of this study is to evaluate the safety and effectiveness of carboplatin compared to the combination of carboplatin and everolimus for the ...

9. lbbc.org lbbc.org/about-breast-cancer/treatments/chemotherapy/types/carboplatin

Carboplatin: Chemotherapy for breast cancer Carboplatin may be used to treat metastatic breast cancer. It can also be used ... Data and Safety Monitoring Board · DCIS · de novo · debulking · deductible ...