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

Study Identifier:
PMD-026-1-001
CT.gov Identifier:
NCT04115306
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

This Phase 2a clinical trial (Dauntless-1) is evaluating the safety, tolerability, pharmacokinetics, and anti-tumor activity of PMD-026 in patients with metastatic or locally advanced (inoperable) RSK2+ breast cancer. PMD-026 is a first-in-class oral kinase inhibitor targeting RSK1–4, tested in combination with standard endocrine therapy. All participants receive both therapies at the recommended Phase 2 dose.

The study includes analysis of archived tumor tissue to assess RSK2 activity through immunohistochemistry (IHC) and explore its correlation with clinical outcomes. Researchers are also evaluating the pharmacokinetics of PMD-026 and the efficacy of the combination in patients with cancer gene mutations such as ER, PI3K, or p53.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Breast Cancers
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Oral PMD-026 in combination with fulvestrant Daily dosing of PMD-026 with fulvestrant dosing according to package insert Intervention: Drug: PMD-026 Investigational Drug Drug: fulvestrant SERDs
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete

Requirements information
Inclusion criteria
  • 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
  • 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)

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Muralidhar Beeram
Status
Recruitment Complete
Condition(s) Treated at Site
Breast Cancers