Immunotherapy for Triple-Negative Breast Cancer

Recruiting at 145 trial locations

Overseen By Reference Study ID Number: CO44194 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, CNS metastases, Autoimmune disease, Cardiovascular 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

Duration: Up to 24 months

83 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to assess the efficacy and safety of a novel immunotherapy candidate, tobemstomig, in combination with nab-paclitaxel, for patients with previously untreated, locally advanced, unresectable or metastatic (Stage IV) programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer (TNBC).

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic corticosteroids and immunosuppressive drugs, at least 2 weeks before starting the study treatment. If you are on any other medications, it's best to discuss with the trial team to see if they are allowed.

Is the immunotherapy treatment generally safe for humans?

Nab-paclitaxel, a component of the treatment, has been studied in various cancers and is generally considered safe, though some patients may experience side effects like those seen in breast cancer and lung cancer studies. These side effects can include reactions to the drug, but the formulation is designed to reduce such risks compared to older versions. ^{1 2 3 4 5}

How is the drug for triple-negative breast cancer different from other treatments?

This treatment combines nab-paclitaxel, pembrolizumab, and a novel bispecific antibody RO7247669, which targets both PD-1 and LAG-3 proteins to enhance the immune system's ability to fight cancer, offering a unique approach compared to existing therapies that typically target only one of these proteins. ^{6 7 8 9 10}

What data supports the effectiveness of this drug for triple-negative breast cancer?

Research shows that combining atezolizumab with nab-paclitaxel improved progression-free survival and overall survival in patients with advanced triple-negative breast cancer, especially those with PD-L1 positive tumors. Additionally, pembrolizumab combined with chemotherapy also demonstrated superior efficacy in similar patient groups. ^{6 7 9 10 11}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with previously untreated, PD-L1-positive, advanced triple-negative breast cancer. Participants must have no prior treatments for their condition, measurable disease per RECIST v1.1 criteria, good performance status (ECOG 0 or 1), adequate organ function, and negative tests for HIV and hepatitis. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

You have tested negative for hepatitis B surface antigen (HBsAg) at the screening.

My breast cancer is advanced, cannot be surgically removed, and lacks HER2, ER, and PgR.

My tumor has been tested and shows PD-L1 expression.

Exclusion Criteria

I don't have any health issues that would make it unsafe for me to take a new drug.

I have not received a live vaccine in the last 28 days.

I haven't taken any immune-boosting drugs in the last 4 weeks or longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tobemstomig or pembrolizumab every 3 weeks, plus nab-paclitaxel on a 3 weeks on, 1 week off schedule, until disease progression or up to 24 months

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nab-Paclitaxel
• Pembrolizumab
• RO7247669

Trial Overview The study compares the effectiveness of a new immunotherapy drug called Tobemstomig combined with Nab-Paclitaxel versus Pembrolizumab (an existing treatment) plus Nab-Paclitaxel in treating advanced triple-negative breast cancer that expresses PD-L1.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

Participants will receive tobemstomig every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.

Group II: Arm B Active Control 2 Interventions

Participants will receive pembrolizumab every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.

Nab-Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer

Approved in European Union as Abraxane for:

• Breast cancer
• Pancreatic cancer

Approved in Canada as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

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]

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 study involving 614 patients with advanced triple-negative breast cancer, the SP142 assay identified 46.4% of patients as PD-L1 positive, while the SP263 and 22C3 assays identified significantly higher rates of 74.9% and 73.1%, respectively, indicating that different assays can yield varying results in PD-L1 positivity.

The clinical efficacy of atezolizumab plus nab-paclitaxel was primarily observed in patients who were double-positive for SP142 and either SP263 or 22C3, suggesting that the SP142 assay may be more predictive of treatment benefit compared to the other assays, despite the latter identifying more patients as PD-L1 positive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer. Rugo, HS., Loi, S., Adams, S., et al.[2023]

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]

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

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 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]

Citations

1. 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]

2. 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]

3. 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]

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

PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer. [2023]

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

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

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

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]

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

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04). [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

A phase II, multicenter, single-arm study of tri-weekly low-dose nanoparticle albumin-bound paclitaxel chemotherapy for patients with metastatic or recurrent breast cancer. [2022]

10. 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]

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]