PMD-026 for Breast Cancer

(Dauntless-1 Trial)

Recruiting at 14 trial locations

Overseen By Joseph Leveque, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Phoenix Molecular Designs

Must be taking: Endocrine therapy

Must not be taking: Chemotherapy, Biological therapy

Disqualifiers: Visceral crisis, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

61 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment, PMD-026, to determine its safety and tolerability for individuals with metastatic breast cancer, where the cancer has spread to other parts of the body. PMD-026 targets and kills cancer cells. Participants will receive PMD-026 alongside fulvestrant. Ideal candidates have hormone receptor-positive, HER2-negative breast cancer, have tried at least one hormone therapy, and have experienced cancer progression despite previous treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop endocrine therapy at least 15 days before starting PMD-026. Other medications may need to be stopped if they fall under the exclusion criteria, such as recent chemotherapy or investigational therapy.

Is there any evidence suggesting that PMD-026 is likely to be safe for humans?

Research has shown that PMD-026 is generally safe for people with advanced breast cancer. Studies have found that most patients tolerate the treatment well. Early signs suggest it might be effective. Additionally, results indicate that PMD-026 could slow tumor growth in some patients. Based on these findings, PMD-026 appears safe for further testing in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

PMD-026 is unique because it targets and inhibits a specific protein that fuels the growth of certain breast cancer cells, potentially offering a new way to stop cancer progression. Unlike standard treatments like tamoxifen or aromatase inhibitors, which focus on hormonal pathways, PMD-026 works on a different mechanism that could be more effective for patients who don't respond well to existing therapies. Researchers are excited about PMD-026 because it represents a novel approach, possibly leading to more personalized and effective treatment options for breast cancer patients.

What evidence suggests that PMD-026 might be an effective treatment for metastatic breast cancer?

Research has shown that PMD-026 may help treat advanced breast cancer. In an earlier study, most patients tolerated PMD-026 well, and it reduced the risk of cancer progression or death by 93%. The treatment also stabilized the disease in 44% of patients who had previously tried several other treatments. Patients with certain tumor features (high RSK2) lived without cancer worsening for an average of 4.8 months, compared to just 1.3 months for others. In this trial, participants will receive oral PMD-026 in combination with fulvestrant. These results suggest that PMD-026 could be a promising option for some patients with advanced breast cancer. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with metastatic breast cancer, specifically triple-negative type that's worsened after standard treatments. Participants must have acceptable organ function and blood counts, not be pregnant or breastfeeding, agree to use contraception, and can't have certain infections or uncontrolled high blood pressure.

Inclusion Criteria

I am a woman who can have children and have a negative pregnancy test.

My breast cancer is triple-negative, has spread, and no standard treatments are effective.

I agree not to donate sperm during and for 30 days after the study.

Exclusion Criteria

Your blood pressure is not well controlled, with numbers higher than 180 over 100.

My brain metastases are treated and I've been stable for over 28 days.

I had a minor surgery less than a week ago, but my central catheter was placed without waiting.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily dosing of PMD-026 in combination with fulvestrant according to the package insert

6 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• PMD-026

Trial Overview The trial is testing PMD-026, an oral medication aimed at destroying tumor cells in patients with advanced breast cancer. It examines the drug's safety and how well patients tolerate it. The study involves two parts: dose escalation to find a safe dosage and dose expansion to test its effects further.

How Is the Trial Designed?

Group I: Oral PMD-026 in combination with fulvestrant Experimental Treatment 2 Interventions

Daily dosing of PMD-026 with fulvestrant dosing according to package insert

Who Is Running the Clinical Trial?

Phoenix Molecular Designs

Lead Sponsor

Trials

1

Recruited

60+

Published Research Related to This Trial

Preactivated merocyanine 540 (pMC540) and its active isolate merodantoin significantly inhibited tumor growth in established human breast cancer xenografts, achieving 74% and 84% inhibition respectively in nude mice.

Both compounds demonstrated effectiveness against estrogen-independent breast tumors, indicating their potential as targeted therapies with minimal cytotoxicity to normal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth inhibitory effects of pMC540 and merodantoin on established MCF-7 human breast tumor xenografts. Sharma, R., Gulliya, KS.[2013]

The study found that breast cancer patients treated with selective estrogen receptor modulators (SERMs) had a significantly higher incidence of uterine malignant mixed Müllerian tumors (S-uMMMTs), with a 6.35-fold increase compared to those not treated with SERMs.

Despite the increased incidence of S-uMMMTs in SERM-treated patients, the clinicopathologic features and overall survival rates were similar across S-uMMMTs, non-SERM associated uMMMTs, and de novo uMMMTs, suggesting that while SERMs may contribute to tumor development, they do not significantly alter the disease characteristics or prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics. Jeong, BK., Sung, CO., Kim, KR.[2020]

In a study of 382 breast cancer patients on tamoxifen, those with reduced CYP2D6 activity (≤50% of normal) showed a higher risk of cancer recurrence and breast cancer-specific mortality, indicating the importance of CYP2D6 in treatment outcomes.

The association between CYP2D6 activity and poor outcomes was particularly significant in premenopausal patients, suggesting that genetic testing for CYP2D6 could help tailor tamoxifen therapy in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CYP2D6 and adjuvant tamoxifen: possible differences of outcome in pre- and post-menopausal patients. Margolin, S., Lindh, JD., Thorén, L., et al.[2022]

In a study of 278 breast cancer patients treated with tamoxifen, those with less functional CYP2D6 enzyme variants (heterozygous extensive/intermediate and poor metabolizers) were significantly less likely to experience a greater than 10% reduction in percent mammographic density (PMD), which is linked to breast cancer risk and prognosis.

The results suggest that genetic variations in the CYP2D6 gene may influence how effectively tamoxifen reduces PMD, indicating that genetic testing could help predict treatment responses in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of CYP2D6 metabolizer status with mammographic density change in response to tamoxifen treatment. Li, J., Czene, K., Brauch, H., et al.[2021]

In a study of 94 advanced breast cancer patients, those with at least one functional CYP2D6 allele experienced significantly longer progression-free survival (PFS) and overall survival (OS) compared to those with impaired CYP2D6 activity, highlighting the importance of genetic testing in treatment efficacy.

The clinical benefit rate was notably higher in patients with functional CYP2D6 alleles (73%) compared to those with impaired alleles (38.5%), suggesting that CYP2D6 genotype testing could guide more effective tamoxifen treatment strategies in advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer. Karle, J., Bolbrinker, J., Vogl, S., et al.[2013]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS1130

Dauntless-1, a phase 2 clinical trial to evaluate PMD-026 ... In the Phase 1/1b monotherapy study, PMD-026 was generally well-tolerated, and it reduced the risk of progression or death in patients by 93% in ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO3-29-04/744652/Abstract-PO3-29-04-Patient-selection-for-high-RSK2

Abstract PO3-29-04: Patient selection for high RSK2 ... Patients had a median of 5 prior lines of therapy and PMD-026 achieved stable disease in 44% (11/25) of the subjects.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04115306

NCT04115306 | Phase 1/1b/2 Study of Oral PMD-026 in ... The purpose of this study is to test the safety and tolerability of PMD-026 in patients with metastatic breast cancer. PMD-026 is a targeted oral agent designed ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT297675

First-in-human phase I/Ib multicenter, open-label dose ... Methods: This single-arm, open-label, first-in-human, phase I/Ib study evaluates the safety and efficacy of single agent PMD-026 in patients with metastatic ...

5. phoenixmd.ca phoenixmd.ca/media-coverage/2025/2/20/phoenix-molecular-designs-dosed-first-patient-in-dauntless-1-a-phase-2-clinical-trial-of-pmd-026-in-combination-with-fulvestrant-for-rsk2-high-breast-cancer

PMD-026 is a first-in-class and best ... Moreover, PMD-026 demonstrated a median progression free survival (mPFS) of 4.8 months in patients with RSK2-high tumors versus only 1.3 months ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e13043

First-in-human phase 1/1b expansion of PMD-026, an oral ... PMD-026 also demonstrated a tolerable safety profile and initial signs of efficacy in patients with metastatic breast cancer. The intensity of ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/phoenixmd-concludes-enrolment-trial/

PhoenixMD concludes enrolment in Phase I/Ib breast ... Phase I results showed that PMD-026 demonstrated to be well-tolerated in patients with breast cancer and could hinder tumour growth for up to ...