Zelenectide Pevedotin for Breast Cancer

Recruiting at 35 trial locations

Overseen By BicycleTx Limited

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BicycleTx Limited

Must not be taking: MMAE therapies, CYP3A inhibitors

Disqualifiers: HER2-positive, CNS metastases, 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 approximately 3 years

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zelenectide pevedotin for individuals with specific types of advanced breast cancer. The goal is to evaluate the treatment's effectiveness and safety for those whose cancer cannot be removed or has spread, and who have already tried other treatments. The trial includes two groups: one for individuals with hormone receptor-positive breast cancer and another for those with triple-negative breast cancer. Candidates may be suitable if their breast cancer has a specific gene change and previous treatments have not succeeded. 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 any systemic anticancer therapy at least 28 days before starting the study treatment. Additionally, you cannot take medications that strongly affect certain liver enzymes (CYP3A) or P-glycoprotein while on the study.

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

Research has shown that zelenectide pevedotin is generally safe for patients with advanced solid tumors, including breast cancer. In earlier studies, patients tolerated this treatment well, and it demonstrated promising effects against tumors. For those with triple-negative breast cancer (TNBC), zelenectide pevedotin was particularly effective, especially in patients with a specific gene change called NECTIN4 amplification.

For patients with hormone receptor-positive and HER2-negative breast cancer, the treatment also proved safe. The recommended doses were generally well-tolerated. Although zelenectide pevedotin remains under study, early results suggest it is safe for humans, indicating its potential as a treatment option for breast cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Zelenectide Pevedotin is unique because it offers a novel approach to treating breast cancer, particularly for those with triple-negative breast cancer (TNBC) and HR+/HER2-negative breast cancer. Unlike standard treatments like chemotherapy, which can affect both cancerous and healthy cells, Zelenectide Pevedotin is designed to specifically target and deliver treatment directly to cancer cells, potentially reducing side effects. Researchers are excited about its targeted mechanism of action, which may improve outcomes by more effectively attacking cancer cells while sparing healthy tissue. This targeted approach represents a promising advancement in precision medicine for breast cancer patients.

What evidence suggests that zelenectide pevedotin might be an effective treatment for breast cancer?

Research shows that zelenectide pevedotin has promising results for treating certain types of breast cancer. In this trial, participants will be divided into two cohorts. Cohort B will include those with triple-negative breast cancer (TNBC), where studies have found that this treatment effectively slows or stops tumor growth. Cohort A will include patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-negative) breast cancer, where earlier research also showed potential, with zelenectide pevedotin being safe and initially effective in shrinking tumors. This drug targets NECTIN4, a protein often found in high levels in these cancers, which helps it attack cancer cells more effectively. These findings suggest that zelenectide pevedotin could be a promising option for people with these specific types of breast cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people with advanced breast cancer that has come back or spread and can't be removed by surgery. Participants must have a life expectancy of at least 12 weeks, be relatively active (able to care for themselves), and have measurable disease. They need confirmed NECTIN4 gene amplification and should have received some prior therapy but not too much: up to 3 treatments if their cancer grows despite hormone therapy, or between 1-3 treatments if they have triple-negative breast cancer.

Inclusion Criteria

I can provide tissue samples for gene testing from my advanced breast cancer.

My cancer can be measured by standard health scans.

I can do most of my daily activities on my own.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zelenectide pevedotin for NECTIN4-amplified advanced breast cancer

Up to approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Zelenectide Pevedotin

Trial Overview

The study is testing Zelenectide pevedotin on two groups of patients with advanced breast cancer: those whose tumors grow despite hormone therapy (HR+/HER2-) and those with triple-negative breast cancer. It's an open-label study, meaning everyone knows what treatment they're getting, aiming to see how effective and safe this new drug is.

How Is the Trial Designed?

Group I: Cohort B (TNBC) Experimental Treatment 1 Intervention

Group II: Cohort A (HR+/HER2-negative breast cancer) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

BicycleTx Limited

Lead Sponsor

Trials

5

Recruited

1,800+

Published Research Related to This Trial

In a phase II trial involving 76 patients with HER2/neu-negative metastatic breast cancer, the combination of docetaxel and bevacizumab showed a promising objective response rate of 51%, with a median overall survival of 26.3 months.

The treatment was generally well tolerated, with manageable side effects, although common grade 3/4 adverse events included neutropenia (33%) and leukopenia/lymphopenia (25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). Hurvitz, SA., Allen, HJ., Moroose, RL., et al.[2020]

The novel 2'-behenoyl-paclitaxel (C22-PX) nanoparticle formulation showed better tolerance and higher plasma and tumor concentrations compared to traditional Taxol in a mouse model of metastatic breast cancer.

The NP formulation of C22-PX resulted in significantly improved antitumor efficacy, indicating its potential as a more effective treatment option for metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2'-Behenoyl-paclitaxel conjugate containing lipid nanoparticles for the treatment of metastatic breast cancer. Ma, P., Rahima Benhabbour, S., Feng, L., et al.[2021]

Adjuvant chemotherapy significantly improves survival in node-positive breast cancer patients, with a 23.5% reduction in recurrence and a 15% reduction in mortality, particularly benefiting hormone receptor-negative patients more than receptor-positive ones.

Tamoxifen, while effective, may reduce the efficacy of chemotherapy in hormone receptor-positive patients by inducing the anti-apoptotic gene Bcl-2, which can lead to decreased drug sensitivity, suggesting that chemotherapy should precede tamoxifen treatment for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pitfall in the survival benefit of adjuvant chemotherapy for node- and hormone receptor-positive patients with breast cancer: the paradoxical role of Bcl-2 oncoprotein (review). Kim, R., Osaki, A., Toge, T.[2019]

In the E2100 phase III trial involving patients with HER2-negative metastatic breast cancer, the combination of paclitaxel and bevacizumab significantly improved progression-free survival (PFS) compared to paclitaxel alone, with median PFS increasing from 5.8 months to 11.3 months.

The overall response rate (ORR) also more than doubled with the addition of bevacizumab, rising from 22.2% to 48.9%, demonstrating a strong therapeutic effect of this combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. Gray, R., Bhattacharya, S., Bowden, C., et al.[2022]

In a retrospective analysis of 40 women with metastatic breast cancer treated with albumin-bound paclitaxel and bevacizumab, there was an overall response rate of 48.5%, with 16 out of 33 women showing objective responses (3 complete and 13 partial).

The treatment was well tolerated, with common side effects including fatigue, neuropathy, pain, and hypertension, suggesting that this combination could be a safer option for patients compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and albumin-bound paclitaxel treatment in metastatic breast cancer. Link, JS., Waisman, JR., Nguyen, B., et al.[2015]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06840483

NCT06840483 | Study of Zelenectide Pevedotin in ...

This is a global, multicenter, open-label study that aims to assess the efficacy and safety of zelenectide pevedotin in participants with NECTIN4-amplified ...

2.

targetedonc.com

targetedonc.com/view/zelenectide-pevedotin-shows-safety-preliminary-efficacy-in-advanced-solid-tumors

Zelenectide Pevedotin Shows Safety, Preliminary Efficacy ...

Zelenectide pevedotin showed a favorable safety profile and promising antitumor activity in advanced solid tumors, especially urothelial ...

3.

aacrjournals.org

aacrjournals.org/clincancerres/article/31/12_Supplement/P4-10-21/753923/Abstract-P4-10-21-Enhanced-anti-tumor-activity-of

Enhanced anti-tumor activity of zelenectide pevedotin in triple ...

Enhanced anti-tumor activity of zelenectide pevedotin in triple negative breast cancer ... Lung Cancer Survival Up 26% Over Last 5 Years.

4.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/578464

Study to Assess Clinical Activity of Zelenectide Pevedotin ...

This is a global, multicenter, open-label study that aims to assess the efficacy and safety of zelenectide pevedotin in participants with ...

5.

esmoopen.com

esmoopen.com/article/S2059-7029(25)00854-3/fulltext

414TiP Phase I/II study (Duravelo-1) of zelenectide ...

Preliminary antitumor activity and a tolerable safety profile have been shown with zele in patients (pts) with solid tumors, including breast cancer (BC).

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO-25-00559

First-in-Human, Phase I/II Dose Escalation and Expansion ...

The recommended Phase II doses of zelenectide pevedotin were generally well tolerated, with the incidence of monomethyl auristatin E (MMAE)– ...

7.

investors.bicycletherapeutics.com

investors.bicycletherapeutics.com/static-files/230ee54a-bf10-4723-af6d-da1844278853

Zelenectide Pevedotin Program Update

TCGA study abbreviations: Triple Negative Breast Cancer (TNBC) was selected by filtering Breast Cancer (BRCA) patients with ER, PR and HER2 ...