Vericiguat for Breast Cancer-Related Heart Failure

Overseen By Jennifer Liu, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Nitrates, Phosphodiesterase inhibitors

Disqualifiers: Hypertrophic cardiomyopathy, Uncontrolled arrhythmia, Severe hepatic insufficiency, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding vericiguat, a medication, to the usual treatment for heart issues caused by breast cancer therapy can improve heart function. Researchers seek to discover whether this combination is better, the same, or worse than the standard approach. Participants should have breast cancer and related heart problems from prior treatments that affect their daily lives. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use long-acting nitrates, NO donors, or phosphodiesterase inhibitors while participating.

Is there any evidence suggesting that vericiguat is likely to be safe for humans?

Research shows that vericiguat can lower the risk of death from heart problems and reduce hospital visits for heart failure patients. The FDA has approved it for treating heart failure, confirming its safety for use. Earlier studies found that vericiguat can decrease certain signs of heart failure, potentially benefiting patients. While these findings are encouraging, all medications can have side effects. Participants in clinical trials might react differently, so staying informed and discussing any concerns with healthcare providers is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Vericiguat is unique because it targets a different pathway in treating heart failure related to breast cancer. Most treatments for heart failure, like ACE inhibitors and beta-blockers, focus on managing symptoms and improving heart function. But Vericiguat works by enhancing the nitric oxide-sGC-cGMP pathway, which helps relax blood vessels and improve blood flow. This new mechanism may offer hope for better outcomes in patients who haven't responded well to standard treatments. Researchers are excited because it could provide a more effective option for those struggling with heart failure due to breast cancer.

What evidence suggests that vericiguat might be an effective treatment for heart failure related to breast cancer?

Research shows that vericiguat, which participants in this trial may receive, can improve heart function in people with heart failure. Studies have found that it helps the heart pump more blood and eases blood flow through vessels, enhancing heart performance. In earlier trials, vericiguat reduced major heart-related problems in heart failure patients. For those with breast cancer who have heart issues from treatment, vericiguat might improve heart and lung fitness. The U.S. FDA has already approved vericiguat to lower the risk of heart failure complications. These findings suggest vericiguat could effectively improve heart health for those with cancer-related heart problems. ^{1 2 3 4 6}

Who Is on the Research Team?

Anthony Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with biopsy-proven breast cancer and heart issues due to past cancer treatments. They must have a specific decrease in heart function, be able to do an exercise test, and use effective birth control if needed. People can't join if they have severe kidney, liver, lung diseases or other conditions that could interfere with the study.

Inclusion Criteria

My breast cancer diagnosis was confirmed through a biopsy.

I agree to use effective birth control during and for 30 days after the study.

My heart function has worsened due to cancer treatment.

Exclusion Criteria

I am currently using or plan to use a phosphodiesterase inhibitor.

I do not have any major heart, lung, or mental health issues that prevent me from exercising.

I do not have severe kidney, liver, or lung problems, or any other condition that would stop me from completing the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vericiguat or optimal medical therapy for cancer therapy-related cardiac dysfunction

6 months

Regular titration visits for dose adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vericiguat

Trial Overview The trial tests whether adding Vericiguat to standard heart failure treatment helps improve heart function in breast cancer patients who've developed cardiac dysfunction from previous cancer therapy better than standard treatment alone.

How Is the Trial Designed?

Group I: Vericiguat plus optimal medical therapy Experimental Treatment 1 Intervention

For patients randomized to vericiguat, a starting dose of 2.5mg will be initiated at the randomization visit. At pre-specified titration visits, subjects will be up-titrated to vericiguat 5mg and then to the target dose of vericiguat 10mg using titration criteria based on mean systolic blood pressure and evaluation for clinical symptoms. Vericiguat will be administered in the background of optimal medical therapy for cardiomyopathy/heart failure.

Group II: Optimal medical therapy Active Control 1 Intervention

For patients randomized to the control group, optimal medical therapy for cardiomyopathy/heart failure will be instituted throughout the study period.

Vericiguat is already approved in United States, European Union for the following indications:

Approved in United States as Verquvo for:

• Heart failure

Approved in European Union as Verquvo for:

• Chronic heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 628 women with breast cancer undergoing anthracycline chemotherapy, those receiving continuous statin therapy had a significantly lower risk of developing new-onset heart failure (HF), with a hazard ratio of 0.3, indicating a protective effect of statins.

The study suggests that statins may help prevent cardiotoxicity associated with chemotherapy, aligning with previous animal studies, and highlights the need for further research through prospective clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. Seicean, S., Seicean, A., Plana, JC., et al.[2012]

Echocardiographic surveillance in breast cancer patients treated with anti-HER2 antibodies significantly reduced the incidence of cardiac dysfunction and acute heart failure, with only 2.1% of patients in the surveillance group reaching the composite endpoint compared to 5.5% in the non-surveillance group.

Patients undergoing echocardiographic monitoring were more likely to receive cardioprotective medications, suggesting that regular heart monitoring can lead to timely interventions that improve cardiac safety during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of surveillance by echocardiography for cancer therapeutics-related cardiac dysfunction of patients with breast cancer. Okushi, Y., Saijo, Y., Yamada, H., et al.[2023]

Cancer patients are at risk of developing heart failure due to the combined effects of anticancer treatments, existing cardiovascular conditions, and the cancer itself, which can complicate treatment and worsen prognosis.

Recent guidelines from American and European cardiology organizations emphasize the importance of a multidisciplinary approach (cardio-oncology) to manage heart failure in cancer patients before and during cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of American and European guidelines for cardio-oncology of heart failure. Chen, JZ., Liang, B.[2023]

Breast and childhood cancer survivors are at increased risk of end-stage heart failure due to cardiotoxic treatments like anthracyclines and trastuzumab, with predictors of irreversible heart failure including age, renal dysfunction, and HER2 positivity.

Left ventricular assist devices (LVAD) and cardiac transplantation are viable options for treating chemotherapy-induced heart failure, with good long-term survival rates, although careful patient selection is crucial due to complications like right ventricular dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Advanced Heart Failure due to Cancer Therapy: the Present Role of Mechanical Circulatory Support and Cardiac Transplantation. Deo, SV., Al-Kindi, SG., Oliveira, GH.[2020]

Cardiovascular events are a major concern for cancer survivors, as they can lead to significant health issues and impact cancer treatment options, particularly due to cancer therapeutics-related cardiac dysfunction (CTRCD).

Recent guidelines for managing CTRCD are primarily based on data from heart failure patients without cancer, highlighting a need for more specific research on cardioprotective strategies for newer cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chemotherapy-associated cardiomyopathy. Cai, AW., Taylor, MH., Ramu, B.[2020]

Citations

1. withpower.com withpower.com/trial/phase-2-breast-neoplasms-3-2023-98167

Vericiguat for Breast Cancer-Related Heart Failure The purpose of this study is to find out if adding vericiguat to standard treatment for cancer therapy related cardiac dysfunction (CTRCD) is more effective ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9789902/

Vericiguat: A New Hope for Heart Failure Patients - PMC Overall, oral administration of vericiguat has been found to increase cardiac output and index and to decrease systemic vascular resistance. Vericiguat is not ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05719

A Study of Vericiguat in People With Breast Cancer and ... Giving vericiguat may improve cardiorespiratory fitness in patients with breast cancer and cancer therapy related cardiac dysfunction.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11047880/

Potential Benefits for Anthracycline-Treated Cancer Patients Randomized clinical trials clearly indicate that vericiguat reduced MACE in patients with heart failure at reduced ejection fraction.

5. merck.com merck.com/news/merck-announces-u-s-fda-approval-of-verquvo-vericiguat/

Merck Announces U.S. FDA Approval of VERQUVO® ... VERQUVO was superior to placebo in reducing the risk of cardiovascular death or heart failure hospitalization based on a time-to-event analysis.

6. news-medical.net news-medical.net/news/20250901/Vericiguat-reduces-mortality-and-hospitalizations-in-a-broad-range-of-patients-with-HFrEF.aspx

Vericiguat reduces mortality and hospitalizations in a broad ... In the pooled population, vericiguat significantly reduced the composite endpoint of cardiovascular mortality or HF hospitalization vs. placebo ...