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

Trial Summary

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.

What data supports the effectiveness of the drug combination for breast cancer?

Research shows that combining drugs that block certain proteins (PD-1/PD-L1) can lead to significant benefits for some breast cancer patients, even though the response is modest for most. Additionally, similar drug combinations have shown increased survival times in other studies, suggesting potential benefits for this treatment. ^{1 2 3 4 5}

Is Sacituzumab Govitecan safe for humans?

Sacituzumab Govitecan has been studied for safety in patients with breast cancer and other solid tumors. Common side effects include diarrhea, neutropenia (low white blood cell count), nausea, and fatigue. Serious side effects like colitis (inflammation of the colon), pneumonitis (lung inflammation), and sepsis (a severe infection) have been reported, so close monitoring is recommended. ^{6 7 8 9 10}

How is the drug combination of Nivolumab, Relatlimab FDC + Nivolumab, and Sacituzumab Govitecan unique for breast cancer treatment?

This drug combination is unique because it includes Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, and Sacituzumab Govitecan, which delivers chemotherapy directly to cancer cells. This combination may offer a novel approach by targeting cancer cells in multiple ways, potentially improving treatment effectiveness for breast cancer. ^{4 11 12 13 14}

What is the purpose of this trial?

This is a randomized, open-label, phase Ib study to assess safety and efficacy of sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus a fixed dose combination of nivolumab and relatlimab in patients with programmed cell death-ligand 1 (PD-L1) positive (defined by combined positive score \>10), metastatic, triple negative breast cancer on routine testing with one prior line of cytotoxic chemotherapy with pembrolizumab in the metastatic setting. The study treatment will be continued until the progression of disease, unacceptable toxicity, death, or withdrawal of consent for any reason.

Research Team

Adriana Kahn, MD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 (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]

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]

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]

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]

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]

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]

References

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

Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer. [2023]

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

Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B). [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging combination immunotherapy strategies for breast cancer: dual immune checkpoint modulation, antibody-drug conjugates and bispecific antibodies. [2022]

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

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

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

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

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

Role of sacituzumab govitecan in solid tumors. [2023]

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

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023]

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

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. [2021]

11. Ireland pubmed.ncbi.nlm.nih.gov

Does nivolumab for progressed metastatic lung cancer fulfill its promises? An efficacy and safety analysis in 20 general hospitals. [2021]

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

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. [2022]

13. 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]

14. Denmark pubmed.ncbi.nlm.nih.gov

Atezolizumab and nab-paclitaxel for advanced breast cancer in Danish real-world patients. [2023]