Nab-Paclitaxel + Atezolizumab for Triple Negative Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Metastatic disease, 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

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

Compensation: Varies

Number of Visits: 14

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well nab-paclitaxel and atezolizumab before surgery work in treating patients with triple negative breast cancer (breast cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 protein). Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nab-paclitaxel and atezolizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. This drug combination before surgery may be an effective treatment for triple negative breast cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic immunosuppressive medications or certain other treatments, you may need to stop them before participating. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab plus Nab-Paclitaxel for treating triple-negative breast cancer?

Research shows that combining Atezolizumab with Nab-Paclitaxel significantly improved progression-free survival (the time during which the cancer does not get worse) in patients with advanced triple-negative breast cancer, especially in those with PD-L1-positive tumors. This combination is approved for use in several regions based on these findings. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Nab-Paclitaxel safe for humans?

The combination of Atezolizumab and Nab-Paclitaxel has been studied for safety, showing common side effects like low white blood cell counts, nerve damage, and immune-related issues such as skin rash and thyroid problems. Atezolizumab has also been linked to rare cases of hemolytic anemia (a condition where red blood cells are destroyed faster than they can be made). ^{1 2 3 6 7}

How is the drug combination of Atezolizumab and Nab-Paclitaxel unique for treating triple-negative breast cancer?

The combination of Atezolizumab and Nab-Paclitaxel is unique because it is the first immunotherapy approved for advanced triple-negative breast cancer, specifically targeting tumors with PD-L1 expression. This combination enhances the anticancer activity and has shown to prolong progression-free survival compared to standard treatments. ^{1 2 3 4 8}

Research Team

Clinton Yam, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for women with triple negative breast cancer who haven't had certain treatments. They must have a tumor of at least 1.5 cm or a lymph node over this size, be able to get pregnant and agree to use contraception, and have no prior malignancies within the last 5 years except some skin cancers or cervical carcinoma in situ.

Inclusion Criteria

Signed written informed consent

My cancer is mostly not driven by estrogen, progesterone, or HER2.

My breast cancer is confirmed and the tumor is at least 1.5 cm or I have a lymph node larger than 1.5 cm.

Exclusion Criteria

Concurrent disease or condition that would interfere with study participation or safety, such as any of the following

I am not pregnant or breastfeeding.

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Patients receive atezolizumab and nab-paclitaxel intravenously. Treatment repeats every 21 days for 4 cycles.

12 weeks

4 cycles (in-person)

Surgery

Patients undergo definitive breast surgery within 6 weeks of the completion of neoadjuvant treatment.

6 weeks

Adjuvant Treatment

Within 4 weeks after surgery, patients receive atezolizumab intravenously. Treatment repeats every 21 days for 4 cycles.

12 weeks

4 cycles (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 3 years

Every 6 months

Treatment Details

Interventions

• Atezolizumab
• Nab-paclitaxel

Trial Overview The study tests nab-paclitaxel combined with atezolizumab before surgery in patients with triple negative breast cancer. It aims to see if this drug combo can shrink tumors effectively enough to reduce the amount of tissue removed during surgery.

Participant Groups

Group I: Treatment (atezolizumab, nab-paclitaxel) Experimental Treatment 2 Interventions

NEOADJUVANT: Patients receive atezolizumab IV over 60 minutes on day 1 and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo definitive breast surgery within 6 weeks of the completion of treatment. ADJUVANT: Within 4 weeks after surgery, patients receive atezolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a phase 3 trial involving 902 patients with untreated metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel significantly improved progression-free survival compared to nab-paclitaxel alone, with median survival times of 7.2 months versus 5.5 months, respectively.

The combination therapy also showed promising overall survival results, particularly in patients with PD-L1-positive tumors, where median overall survival was 25.0 months for the combination versus 15.5 months for the placebo group, indicating enhanced efficacy without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. Schmid, P., Adams, S., Rugo, HS., et al.[2021]

Atezolizumab, when used with nab-paclitaxel for treating triple negative breast cancer, can cause rare side effects like autoimmune hemolytic anemia, as seen in a case study of a 59-year-old female patient.

The patient's hemolytic anemia was effectively managed with a high-dose prednisone taper, allowing her to continue her cancer treatment without further complications through multiple cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. Younce, CM., Lawton, JM., Patel, DR.[2021]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

In the IMpassion131 trial involving 651 patients with advanced triple-negative breast cancer, adding atezolizumab to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS) compared to paclitaxel alone, indicating that this combination may not provide the expected benefits in treatment outcomes.

While the addition of atezolizumab showed a higher unconfirmed overall response rate and longer duration of response in the PD-L1-positive population, the overall survival results were similar between the two treatment groups, suggesting that the combination therapy does not significantly enhance long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Miles, D., Gligorov, J., André, F., et al.[2021]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

In a study of 81 women with early-stage estrogen receptor-positive breast cancer, nab-Paclitaxel showed significant antitumor activity with a good response rate (RCB 0+I) of 24.7%, indicating its effectiveness as a neoadjuvant treatment despite a higher than expected poor response rate (RCB III) of 28.4%.

The treatment was associated with low rates of severe toxicity, with neutropenia being the most common side effect, and an exploratory analysis suggested that overexpression of the SPARC protein in tumors may predict a complete response, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. Martín, M., Chacón, JI., Antón, A., et al.[2021]

References

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

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. [2021]

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

Atezolizumab-induced hemolytic anemia - A case report. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]

4. 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]

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

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. [2021]

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

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

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

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. [2021]