Phase 1/1b/2 Study of Oral PMD-026 in Patients With Metastatic Breast Cancer (Dauntless-1)

January 18, 2026 updated by: Phoenix Molecular Designs

Ph 1/1b/2 Multicenter, Open-Label, FIH Dose Esc & Dose Exp Study to Assess Safety and Tolerability of Orally Administered PMD-026 as a Single Agent and in Combination in Patients With Metastatic or Locally Advanced (Inoperable) RSK2+ Breast Cancer

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 to kill tumor cells in metastatic breast cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Combination with fulvestrant (Part 3):

This study will enroll RSK2+, HR+, and human epidermal growth factor receptor 2 negative (HER2-) patients to evaluate PMD-026 in combination with a standard dose and schedule of fulvestrant. Fulvestrant will be dosed per the package insert in combination with PMD-026 at the RP2D determined in the monotherapy phase of the study. Up to 20 patients will be enrolled with locally advanced or metastatic HR+/HER2- breast cancer previously treated with a CDK4/6 inhibitor in combination with endocrine therapy.

Study Type

Interventional

Enrollment (Estimated)

61

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Principal Investigator:
          • Hope Rugo, MD
        • Contact:
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope Orange County, Lennar
        • Principal Investigator:
          • Hope Rugo, MD
        • Contact:
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles (UCLA)
        • Contact:
        • Principal Investigator:
          • Nicolaos Palaskas, MD
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Hyo Han, MD
        • Contact:
    • Illinois
      • Zion, Illinois, United States, 60099
        • Recruiting
        • City of Hope Chicago
        • Principal Investigator:
          • Ajaz Khan, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital Cancer Center
        • Principal Investigator:
          • Seth Wander, MD
        • Contact:
    • Michigan
    • Ohio
      • Columbus, Ohio, United States, 43210
    • Texas
      • Houston, Texas, United States, 77030
        • Withdrawn
        • Oncology Consultants
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • South Texas Accelerated Research Therapeutics
        • Contact:
        • Principal Investigator:
          • Muralidhar Beeram, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria, Combination with fulvestrant (Part 3):

  • RSK2 positive from available archival or fresh tumor tissue (FFPE).
  • Histologically or cytologically diagnosed HR+, HER2-
  • ESR1 wild type
  • Diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amendable to resection or radiation with curative intent or metastatic disease not amendable to curative therapy
  • Must be appropriate candidates for endocrine therapy
  • Previously received at least 1 line of endocrine therapy for MBC or had recurrence while on adjuvant endocrine therapy for locally advanced breast cancer
  • Discontinued endocrine therapy at least 15 days prior to first dose of PMD-026
  • At least 1 measurable target lesion as defined by RECIST v1.1
  • Progression on or after treatment with a CDK4/6 inhibitor in combination with endocrine therapy inhibitor in the locally advanced or metastatic setting
  • Adequate hematologic, hepatic, and renal function as assessed by laboratory parameters
  • Toxicity related to prior therapy resolved to at least Grade 1 (alopecia excepted) or to at least Grade 2 with prior approval of the Medical Monitor

Exclusion Criteria, Combination with fulvestrant (Part 3):

  • Prior chemotherapy
  • ESR1 mutations
  • ≤14 days from biological or investigational therapy
  • Presence of visceral crisis or uncontrolled visceral disease for which chemotherapy would be indicated
  • Central nervous system metastases, unless appropriately treated and neurologically stable
  • History of leptomeningeal metastases
  • Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  • Known hepatitis B or hepatitis C infection
  • Known HIV-positive with CD4+ cell counts <350 cells/μL
  • Known HIV-positive with a history of an AIDS-defining opportunistic infection
  • History of clinically significant cardiovascular abnormalities, including QTcF interval >460 msec (using Fridericia's formula)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral PMD-026 in combination with fulvestrant
Daily dosing of PMD-026 with fulvestrant dosing according to package insert
Drug: PMD-026
Investigational Drug
Drug: fulvestrant
SERDs
Other Names:
  • Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of PMD-026 in combination with fulvestrant in patients with HR+/HER2- previously treated breast cancer
Time Frame: 6 weeks
Incidence of AEs, DLTs, SAEs. Changes in laboratory, vital signs, and ECG values.
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma concentration of PMD-026 when administered in combination with fulvestrant
Time Frame: As determined by PK data
The plasma concentration will be measured as part of pharmacokinetic (PK) testing.
As determined by PK data
Preliminary anti-tumor activity of PMD-026 when dosed in combination with fulvestrant
Time Frame: Until PD or death, up to 2 years
ORR, DOR, DCR, PFS
Until PD or death, up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess OS
Time Frame: Throughout study
OS defined as time from first dose to death
Throughout study
Evaluate QT interval and PMD-026 concentrations
Time Frame: Throughout study
Qualitative and/or quantitative associations of PK parameter concentrations with QTcF changes
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phoenix Molecular Designs

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2019

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

October 2, 2019

First Submitted That Met QC Criteria

October 2, 2019

First Posted (Actual)

October 4, 2019

Study Record Updates

Last Update Posted (Actual)

January 21, 2026

Last Update Submitted That Met QC Criteria

January 18, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMD-026-1-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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