Immunotherapy for Triple-Negative Breast Cancer

Not currently recruiting at 157 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment combined with a chemotherapy drug to evaluate its efficacy and safety for individuals with triple-negative breast cancer (TNBC). The trial includes two groups: one group receives tobemstomig (an anti-PD-1/anti-LAG-3 bispecific antibody) with nab-paclitaxel (a chemotherapy drug), while the other group receives pembrolizumab (an immunotherapy drug) with nab-paclitaxel. It targets individuals with advanced TNBC that cannot be surgically removed or has metastasized, who have not received prior systemic treatment for this condition. Participants must have a type of TNBC positive for the PD-L1 protein, verified through a specific test. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

Studies have shown that the treatment tobemstomig, when combined with nab-paclitaxel, is generally well-tolerated. Research on similar drugs targeting PD-1 and LAG-3 has demonstrated their safety both alone and with other cancer treatments, suggesting that tobemstomig might be similarly safe.

For pembrolizumab combined with nab-paclitaxel, safety information is also available. Previous studies found that while some immune-related side effects occurred, they were rare. For example, serious side effects leading to death occurred in only 0.3% of patients. The FDA has already approved this combination for treating triple-negative breast cancer, indicating it is considered safe for this use.

While both treatments have shown promise in terms of safety, individual experiences can vary. Discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for triple-negative breast cancer because they incorporate novel mechanisms and combinations that could enhance effectiveness. RO7247669 is a new investigational drug that may offer unique benefits over existing therapies. Unlike standard treatments like chemotherapy, this approach combines nab-paclitaxel with pembrolizumab, a powerful immunotherapy known for harnessing the body's immune system to target cancer cells. This combination aims to improve patient outcomes by potentially increasing the immune system's ability to fight tumors.

What evidence suggests that this trial's treatments could be effective for triple-negative breast cancer?

In this trial, participants will receive different treatment combinations for triple-negative breast cancer (TNBC). Research has shown that combining pembrolizumab with chemotherapy, such as nab-paclitaxel, effectively treats TNBC. Studies indicate that this combination, which participants in Arm B of this trial will receive, can improve survival rates and reduce the risk of the cancer spreading or worsening by 35%. Meanwhile, early research on tobemstomig, which participants in Arm A will receive, suggests it might also be effective by targeting PD-1 and LAG-3, proteins that help cancer cells evade the immune system. Although less information exists on tobemstomig, its approach shows promise for fighting TNBC. Both treatments enhance the immune system's ability to attack cancer, offering hope for those with advanced TNBC. ^{4 6 7 8 9}

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 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 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]

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 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 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 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 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 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]

Citations

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Real-world evidence of the efficacy of neoadjuvant ... Neoadjuvant pembrolizumab has shown efficacy in improving pathologic complete response (pCR) rates and survival outcomes in triple-negative breast cancer (TNBC ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202809

Pembrolizumab plus Chemotherapy in Advanced Triple ... Pembrolizumab monotherapy has shown durable antitumor activity in advanced triple-negative breast cancer, particularly as first-line therapy, ...

3. keytruda.com keytruda.com/triple-negative-breast-cancer/clinical-trial-results/advanced-tnbc/

Triple-negative breast cancer (TNBC) - clinical trials KEYTRUDA + chemotherapy reduced the risk of cancer spreading, growing, or getting worse by 35% compared to placebo + chemotherapy.

4. nature.com nature.com/articles/s41523-025-00814-y

Association of potential biomarkers with clinical outcomes ... In the randomized, phase 3 KEYNOTE-119 study, overall survival (OS) was not significantly improved with pembrolizumab 200 mg Q3W versus ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38597713/

Pembrolizumab plus chemotherapy for first-line treatment ... These results indicate that pembrolizumab + chemotherapy has beneficial effects on patient survival compared with other initial treatment regimens for patients ...

6. keytrudahcp.com keytrudahcp.com/safety/adverse-reactions/triple-negative-breast-cancer/

KEYNOTE-355 - Adverse Reactions & Safety Data Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously.

7. merck.com merck.com/news/pivotal-phase-3-data-for-keytruda-pembrolizumab-in-high-risk-early-stage-triple-negative-breast-cancer-tnbc-published-in-the-new-england-journal-of-medicine/

Pivotal Phase 3 Data for KEYTRUDA® (pembrolizumab) in ... Immune-mediated AEs led to death in 0.3% of patients receiving the KEYTRUDA regimen (n=2) and no patients receiving the chemotherapy-placebo ...

8. keytruda.com keytruda.com/triple-negative-breast-cancer/

Triple-Negative Breast Cancer (TNBC) Learn about an FDA-approved immunotherapy combination treatment for both high-risk early-stage and advanced triple-negative breast cancer (TNBC).

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6816000/

Pembrolizumab in Patients With Advanced Triple-Negative ... Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the ...