Drug Combinations for Breast Cancer

(SIMONE Trial)

Overseen By Stephanie Ladd

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yale University

Must be taking: Cytotoxic chemotherapy

Must not be taking: IV antibiotics, antivirals

Disqualifiers: Pregnancy, Metastatic disease, Cardiac issues, Respiratory illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 10

Duration: Variable (until progression or withdrawal)

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new drug combinations for treating metastatic triple-negative breast cancer that is PD-L1 positive. Researchers aim to assess the safety and effectiveness of these combinations, focusing on sacituzumab govitecan (an antibody-drug conjugate) with either nivolumab (an immunotherapy drug) or a combination of nivolumab and relatlimab. Suitable participants have breast cancer that has spread, is not treatable with surgery, and have already undergone one type of chemotherapy with pembrolizumab. The trial continues until the disease progresses, side effects become unacceptable, or participants choose to leave. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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

The trial information does not specify if you need to stop taking your current medications. However, there is a requirement for an adequate washout period from prior therapies before starting the trial.

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

Research has shown that sacituzumab govitecan is generally well-tolerated by breast cancer patients. In one study, about 22% of patients needed to lower their dose, and 4% had to stop treatment. Only 2% of patients died due to side effects. The most common issues were low white blood cell counts and diarrhea, which sometimes required changes to the treatment plan.

For the combination of sacituzumab govitecan with nivolumab or with a fixed-dose combination of nivolumab and relatlimab, specific safety data is not yet available. As this trial is in an early phase, researchers are closely monitoring safety. Early-phase trials often focus on understanding the safety and tolerability of new treatments, making this a key part of the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a new approach to fighting breast cancer. Unlike the standard chemotherapy and hormone therapy options, these investigational treatments use a combination of immunotherapy and targeted therapy. Sacituzumab govitecan delivers a toxic payload directly to cancer cells, minimizing damage to healthy cells. Combining it with nivolumab and relatlimab enhances the body's immune response against cancer. This unique mechanism of action could potentially improve outcomes for patients with breast cancer beyond what current options offer.

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

Studies have shown that sacituzumab govitecan can significantly improve outcomes for patients with advanced triple-negative breast cancer. It increases the likelihood of cancer shrinking and extends patient survival compared to standard chemotherapy. One study reported that 43% of patients were alive after one year, with an average survival time of about 9.6 months. In this trial, participants in Arm B will receive sacituzumab govitecan plus nivolumab, a drug that boosts the immune system and has shown promising results in improving these outcomes. Participants in Arm A will receive sacituzumab govitecan plus a fixed-dose combination of nivolumab and relatlimab, which may further enhance the immune response, potentially increasing treatment effectiveness. These drugs help the body's immune system fight cancer cells more effectively. ^{3 5 6 7 8}

Who Is on the Research Team?

Adriana Kahn, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of advanced breast cancer (triple-negative, PD-L1 positive) who have had one previous treatment with chemotherapy and pembrolizumab. They must not be pregnant or breastfeeding, willing to use contraception, and free from certain serious health conditions.

Inclusion Criteria

Must have pathologically documented breast cancer that is unresectable/metastatic, HER2-negative, PD-L1 positive, treated with up to one line of systemic cytotoxic chemotherapy with pembrolizumab, prior immune checkpoint inhibition, documented radiologic progression or intolerance to prior therapy, adequate archival tumor sample available for assessment of PD-L1 status, presence or absence of measurable lesion based on CT or MRI, ECOG PS 0 or 1, LVEF ≥50%, adequate laboratory parameters, and adequate contraception when indicated

I can understand and sign the consent form.

Exclusion Criteria

Participants who are pregnant or lactating

Participants of childbearing potential or fertile men unwilling to use effective contraception

I do not have major health issues or conditions that could interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus a fixed dose combination of nivolumab and relatlimab until disease progression, unacceptable toxicity, death, or withdrawal of consent

Variable (until progression or withdrawal)

Days 1 and 8 of every 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor response evaluated every nine weeks

Up to 2 years

Every 9 weeks, with a 135-day follow-up visit and long-term follow-up every 3 months

Long-term follow-up

Participants undergo survival chart review follow-up every three months for two years

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Relatlimab FDC + Nivolumab
• Sacituzumab Govitecan (SG)

Trial Overview The study tests the combination of Sacituzumab Govitecan (SG) with Nivolumab or SG plus Relatlimab-Nivolumab FDC in patients. It's randomized and open-label, meaning participants know which treatment they receive. The goal is to see how safe and effective these combinations are.

How Is the Trial Designed?

Group I: Arm A Active Control 2 Interventions

Sacituzumab govitecan plus a fixed dose combination of nivolumab and relatlimab

Group II: Arm B Active Control 2 Interventions

Sacituzumab Govitecan plus nivolumab

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Sacituzumab govitecan (SG) has been approved in the EU for treating adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have undergone at least two prior systemic therapies, showing significant improvements in progression-free survival (4.8 months vs. 1.7 months) and overall survival (11.8 months vs. 6.9 months) compared to treatment of physician's choice.

The most common side effects of SG include diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation, and vomiting, occurring in more than 30% of patients, indicating that while SG is effective, it also has notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. Michaleas, S., Moreno Oliver, A., Mueller-Berghaus, J., et al.[2022]

In a retrospective study of 74 patients with advanced breast cancer, the combination of atezolizumab and nab-paclitaxel resulted in a median progression-free survival (PFS) of 6.0 months and a median overall survival (OS) of 14.3 months, indicating its effectiveness in a real-world setting.

While the survival outcomes were lower than those reported in the phase III Impassion130 trial, the results still met the efficacy standards observed in similar real-world studies, highlighting the need for careful patient selection for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and nab-paclitaxel for advanced breast cancer in Danish real-world patients. Garly, R., Knoop, A., Jensen, MB., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, showed a tolerable safety profile in 52 patients with advanced non-small-cell lung cancer (NSCLC), with 71% experiencing treatment-related adverse events, primarily fatigue and rash.

The treatment resulted in a confirmed objective response rate of 23%, with some patients achieving ongoing complete responses, and a median overall survival of 19.4 months, indicating its potential as an effective first-line therapy for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Gettinger, S., Rizvi, NA., Chow, LQ., et al.[2022]

Anti-PD-1 and anti-PD-L1 antibodies show modest response rates as standalone treatments for metastatic breast cancer, but they are generally well tolerated and can provide significant, lasting benefits for some patients.

These antibodies can be safely combined with various systemic therapies, including chemotherapy and targeted therapies, as well as radiotherapy, suggesting potential for enhanced effectiveness in treating metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer. Page, DB., Bear, H., Prabhakaran, S., et al.[2023]

Sacituzumab govitecan (SG) is an FDA-approved antibody-drug conjugate that has shown significant efficacy in treating metastatic triple-negative breast cancer, improving health-related quality of life and prolonging progression-free and overall survival in patients who have undergone multiple prior therapies.

Ongoing clinical trials are exploring the potential of SG for broader applications, including neoadjuvant and adjuvant therapies, combinations with immunotherapy, and treatment of various solid tumors, indicating its promise as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. Veeraballi, S., Khawar, Z., Aslam, HM., et al.[2023]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., et al.[2023]

Sacituzumab govitecan received full FDA approval after a phase III trial showed it significantly improves progression-free survival in patients with metastatic triple-negative breast cancer, achieving a median of 5.7 months compared to just 1.7 months with standard chemotherapy.

This treatment is an antibody-drug conjugate that targets the Trop-2 receptor and delivers the active metabolite of irinotecan, SN-38, directly to cancer cells, making it a promising option for patients who have already undergone at least two prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. Fleming, PJ., Karpio, S., Lombardo, N.[2021]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(25)01177-9/fulltext

Effectiveness of sacituzumab govitecan and management ... We describe the real-world effectiveness of SG as 2L+ mTNBC treatment and the proportion of patients with neutropenia and its management.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12165508/

Real-World Clinical Outcomes With Sacituzumab ... The 1-year survival rate was 43% (95% CI, 33 to 52). The median DSS was consistent with the OS (9.6 months [95% CI, 7.8 to 12.9]; Fig 2).

3. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424025498

Phase 2 Open-Label Study of Sacituzumab Govitecan as ... Unfortunately, the prognosis is dismal, with 2-year survival rates of 14% and 22%, respectively, and relapses occurring within 6 months in nearly all patients.

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1683594/full

The efficacy and safety of sacituzumab govitecan in ... SG significantly improved ORR (RR=3.97, 95%CIs: 1.32-11.90) and OS (HR=0.59, 95%CIs: 0.47-0.75) versus single agent chemotherapy in RCTs, with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11511732/

Preliminary results from ASCENT-J02: a phase 1/2 study of ... We report SG safety and efficacy in an open-label, phase 1/2 bridging study in Japanese patients with advanced solid tumors (ASCENT-J02; NCT05101096; jRCT ...

6. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2511734

Sacituzumab Govitecan in Untreated, Advanced Triple- ... Among 558 patients, median progression-free survival was 9.7 months (95% confidence interval [CI], 8.1 to 11.1) with sacituzumab govitecan and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11648803/

Safety profile of sacituzumab govitecan in patients with breast ... Dose reductions and treatment discontinuation were reported in 22 % and 4 % of patients, respectively, and 19 deaths (2 %) were documented. Most ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1101

Prevention of sacituzumab govitecan (SG)-related ... The most common SG-related adverse events (AEs) are neutropenia and diarrhea which can lead to treatment modifications. Granulocyte colony- ...