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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immunotherapy drugs to treat triple negative breast cancer, a type of cancer that lacks certain proteins, making it difficult to treat. The goal is to determine if using nab-paclitaxel (a chemotherapy drug) and atezolizumab (an immunotherapy drug) before surgery can shrink tumors and reduce the need to remove healthy tissue. Individuals diagnosed with triple negative breast cancer who have not received prior treatment may be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that nab-paclitaxel and atezolizumab are likely to be safe for humans?

Research has shown that atezolizumab, a treatment used in this trial, generally has a manageable safety profile. While side effects can occur, they are usually expected and controllable. Atezolizumab has demonstrated promising results in treating triple-negative breast cancer (TNBC), and patients typically tolerate the treatment well.

Past studies have also found nab-paclitaxel to be well-tolerated for TNBC. It has been successfully used to treat patients with this type of cancer. Notably, the FDA has already approved nab-paclitaxel for other conditions, which adds reassurance about its safety.

When used together, both treatments have been studied in patients with TNBC, focusing on effectively managing side effects. This means they have been used enough to know that most people do not experience severe unexpected problems. However, as with any treatment, some side effects can occur, and it’s important to discuss these with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nab-paclitaxel and atezolizumab for treating triple-negative breast cancer because it brings a fresh approach to tackling this challenging condition. Unlike standard chemotherapy options that generally target rapidly dividing cells, atezolizumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells. The combination of these treatments aims to enhance the body's natural defenses while directly attacking cancer cells, potentially leading to more effective outcomes. Additionally, nab-paclitaxel is a nanoparticle formulation of paclitaxel, which may improve drug delivery and reduce side effects. This innovative combination might offer new hope for patients where traditional therapies fall short.

What evidence suggests that nab-paclitaxel and atezolizumab might be an effective treatment for triple negative breast cancer?

Research has shown that combining atezolizumab with nab-paclitaxel can effectively treat triple-negative breast cancer (TNBC). One study found that this combination helped patients with advanced TNBC live longer without disease progression. In this trial, participants will receive both atezolizumab and nab-paclitaxel as part of their treatment regimen. This treatment is also suitable for patients with advanced TNBC that cannot be surgically removed. In everyday medical practice, patients with TNBC who have a specific protein marker called PD-L1 have responded well to this combination. These findings suggest that using atezolizumab and nab-paclitaxel together could help shrink tumors and control cancer spread in TNBC patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinton Yam, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1809615

Atezolizumab and Nab-Paclitaxel in Advanced Triple ...

Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32248356/

Atezolizumab (in Combination with Nab-Paclitaxel)

Atezolizumab plus nab-paclitaxel is a useful immunochemotherapy option for patients with unresectable locally advanced or metastatic TNBC.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10491680/

Real-world ANASTASE study of atezolizumab+nab ...

Our paper reports data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program ...

4.

nature.com

nature.com/articles/s41598-023-40569-9

Atezolizumab and paclitaxel as first line therapy in ...

Atezolizumab and paclitaxel has a limited efficacy in PD-L1-positive aTNBC, especially in patients receiving corticosteroids as comedication before treatment ...

5.

tecentriq.global

tecentriq.global/home/indication/triple-negative-breast-cancer.html

Triple-negative breast cancer - tecentriq

TECENTRIQ in combination with nab-paclitaxel (nab-pac) is indicated for the treatment of adult patients with unresectable locally advanced or metastatic TNBC.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12283416/

Peri-operative atezolizumab in early-stage triple-negative ...

Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47–1.21; disease ...

7.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)00107-8/fulltext

IMpassion132 double-blind randomised phase III trial ...

Data on outcomes in patients with rapidly relapsing TNBC are scarce. •. The phase III IMpassion132 trial enrolled patients with TNBC relapse ...

8.

appliedclinicaltrialsonline.com

appliedclinicaltrialsonline.com/view/tecentriq-trial-post-surgery-triple-negative-breast-cancer

Tecentriq Falls Short in Phase III Trial in Post-Surgery ...

At a median follow up of 32 months, iDFS events were reported in 12.8% of patients in the Tecentriq combination cohort compared to 11.4% ...

9.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37921135/

Efficacy and Safety of Atezolizumab Monotherapy or ...

Atezolizumab showed a manageable safety profile and had promising and durable anti-tumor efficacy in TMBC patients.

10.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2701722

Long-term Clinical Outcomes and Biomarker Analyses of ...

The median overall survival (OS) of patients with metastatic TNBC (mTNBC) is 8 to 13 months. Chemotherapy remains the main treatment for TNBC, ...