Radiation, Immunotherapy, and Chemotherapy for Metastatic Triple Negative Breast Cancer

Overseen By Manali Bhave, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Glucocorticoids, Immunosuppressives

Disqualifiers: CNS disease, Hypercalcemia, Autoimmune, 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: 36

Duration: Up to 1 year

29 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, during the trial, you should not receive other cancer treatments except for specific ones like bisphosphonates or RANK-L inhibitors. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment for metastatic triple-negative breast cancer?

Research shows that combining nab-paclitaxel with gemcitabine or carboplatin has been effective in treating metastatic triple-negative breast cancer, with a median progression-free survival of 9.8 months compared to 7.4 months for other combinations. Additionally, pembrolizumab with chemotherapy has shown better outcomes before surgery in similar cases. ^{1 2 3 4 5}

Is the combination of radiation, immunotherapy, and chemotherapy safe for treating metastatic triple-negative breast cancer?

Research shows that treatments combining pembrolizumab (an immunotherapy drug) with chemotherapy and radiation have manageable safety profiles in patients with metastatic triple-negative breast cancer. These treatments have been tested in various studies and are generally considered safe for human use, although individual experiences may vary. ^{1 5 6 7 8}

What makes the treatment for metastatic triple-negative breast cancer unique?

This treatment combines radiation, immunotherapy, and chemotherapy, including pembrolizumab (an immune system booster), with carboplatin, gemcitabine, and paclitaxel, which are chemotherapy drugs. This combination aims to enhance the body's immune response while directly attacking cancer cells, offering a novel approach compared to standard chemotherapy alone. ^{1 3 9 10 11}

What is the purpose of this trial?

This phase II trial tests how well radiation therapy with pembrolizumab and chemotherapy (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine) works in treating patients with PD-L1 positive triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Carboplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. High dose radiation therapy with pembrolizumab and chemotherapy may effective in treating patients with PD-L1 positive metastatic triple negative breast cancer.

Research Team

Manali Bhave, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for individuals with PD-L1 positive metastatic triple negative breast cancer. Participants should have cancer that has spread from the original site to other body parts. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

I am eligible for radiotherapy, immunotherapy, and taxane chemotherapy.

My cancer is not driven by estrogen or progesterone.

AST, ALT ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases)

Exclusion Criteria

Severe, active co-morbidities

Conditions or abnormalities that may confound trial results

Known hypersensitivity to nab-paclitaxel or excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo radiation therapy once every other day for 3 doses

1 week

3 visits (in-person)

Treatment

Patients receive pembrolizumab and chemotherapy. Cycles repeat every 21 or 28 days depending on chemotherapy regimen

Up to 1 year

Multiple visits (in-person) every 21 or 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks

Follow-up visits every 12 weeks

Treatment Details

Interventions

• Carboplatin
• Gemcitabine
• High Dose Radiation Therapy
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests high dose radiation therapy combined with pembrolizumab (an immunotherapy drug) and chemotherapy drugs (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine). The goal is to see if this combination can effectively kill tumor cells in patients with a specific type of advanced breast cancer.

Participant Groups

Group I: Treatment (radiation, pembrolizumab, chemotherapy) Experimental Treatment 11 Interventions

Patients undergo radiation therapy once every other day for 3 doses. Beginning within 48 hours of their first dose of radiation therapy, patients receive standard of care pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive 1 of 3 standard of care chemotherapy options: nab-paclitaxel IV on days 1, 8, and 15 of each cycle, or paclitaxel IV on days 1, 8, and 15 of each cycle, or carboplatin IV and gemcitabine IV on days 1 and 8 of each cycle. Cycles of nab-paclitaxel and paclitaxel repeat every 28 days and cycles of carboplatin and gemcitabine repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy at baseline and 2 weeks after radiation therapy and also undergo CT scans, bone scans and blood sample collections throughout the trial.

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In the phase III KEYNOTE-522 trial, pembrolizumab combined with chemotherapy showed increased effectiveness as a neoadjuvant treatment for triple-negative breast cancer, leading to a higher rate of pathologic complete response compared to chemotherapy alone.

This benefit was observed regardless of the PD-L1 expression levels in patients, suggesting that pembrolizumab may be a broadly effective option for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

Cisplatin and capecitabine combination therapy showed a response rate of 62.1% in 29 patients with metastatic triple negative breast cancer (TNBC) who had previously progressed after other treatments, indicating its efficacy as a subsequent treatment option.

The therapy was generally well-tolerated, with most side effects being mild to moderate, although some patients experienced significant toxicities such as neutropenia and leukocytopenia, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment]. Li, Q., Xu, B., Li, Q., et al.[2018]

In a phase 2 clinical trial involving 17 patients with metastatic triple-negative breast cancer, the combination of pembrolizumab and radiotherapy showed an overall response rate of 17.6%, with three patients achieving complete responses that lasted up to 108 weeks.

The treatment was found to be safe, with the most common side effects being mild dermatitis, and no treatment-related deaths or severe adverse events reported, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. Ho, AY., Barker, CA., Arnold, BB., et al.[2020]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

In a phase 3 trial involving 902 patients with metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel showed a median overall survival of 21.0 months compared to 18.7 months with placebo, although this difference was not statistically significant in the overall population.

For patients with PD-L1 immune cell-positive tumors, atezolizumab plus nab-paclitaxel demonstrated a significant overall survival benefit, with a median survival of 25.0 months versus 18.0 months for placebo, highlighting its potential as an important treatment option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Schmid, P., Rugo, HS., Adams, S., et al.[2020]

In the IMpassion130 trial, the combination of atezolizumab and nab-paclitaxel (A + nP) significantly improved progression-free survival in patients with metastatic triple-negative breast cancer (mTNBC) without negatively impacting their health-related quality of life (HRQoL).

Patient-reported outcomes showed no significant differences in HRQoL or functioning between the A + nP and placebo plus nab-paclitaxel groups, indicating that the treatment did not worsen symptoms like fatigue or nausea, thus maintaining patients' day-to-day functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer. Adams, S., Diéras, V., Barrios, CH., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. [2022]

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

Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. [2022]

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

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

4. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment]. [2018]

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

A randomized phase 3 trial of Gemcitabine or Nab-paclitaxel combined with cisPlatin as first-line treatment in patients with metastatic triple-negative breast cancer. [2022]

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

Nab-paclitaxel/bevacizumab/carboplatin chemotherapy in first-line triple negative metastatic breast cancer. [2015]

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

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. [2023]

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

First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. [2020]

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

Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer. [2022]