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

Metastatic Breast Cancer Clinical Trial

— Dauntless-1  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04115306
• Other study ID #: PMD-026-1-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 14, 2019
• Est. completion date: March 2026

Study information

• Verified date: May 2024
• Source: Phoenix Molecular Designs
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Combination with fulvestrant (Part 3):

This study will prospectively enroll RSK2+ (≥75% nuclear staining with ≥2+ in staining intensity) 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 (500 mg IM, Day 1 and 15 of the first 28-day cycle, then Day 1 of every cycle thereafter) in combination with PMD-026 at the RP2D (200 mg, PO, Q12h) 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.

The combination regimen will have a safety lead-in cohort of 6 patients. The SRC will review the safety data after the sixth patient has been treated for at least 28 days. If determined to be safe, up to 14 additional patients will receive the combination for a total of 20 patients. A Bayesian safety monitoring rule will be used to evaluate the rate of DLTs during expansion. Specifically, the rule will be applied after data is available for the 6th DLT-evaluable patient.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 61
• Est. completion date: March 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria, Combination with fulvestrant (Part 3):

• Available archival or FFPE

• RSK2 positive (=75% nuclear staining with =2+ in staining intensity) as assessed by central lab from available archival or fresh tumor tissue (FFPE).

• Histologically or cytologically diagnosed HR+, HER2- defined as both

• >1% expression of ER and/or PgR receptor

• = 1+ by IHC for HER2, or FISH negative. If 2+ by IHC for HER2 combined with FISH negative

• 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

• Has not received fulvestrant in the locally advanced or metastatic setting. Note: If prior to study entry, a patient initiates fulvestrant in combination with targeted therapy and becomes intolerant of the targeted therapy before progression, that patient may enroll if PMD-026 is initiated within 48 days of start of fulvestrant and no missed doses of fulvestrant occurred.

• Not eligible for an AKT or PI3K inhibitor

• 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):

• =14 days from prior chemotherapy, biological or investigational therapy

• Prior fulvestrant in the locally advanced or metastatic setting

• 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)

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• PMD-026
Investigational Drug
• fulvestrant
SERDs

Locations

Country	Name	City	State
United States	Ohio State University	Columbus	Ohio
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Phoenix Molecular Designs

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess OS	OS defined as time from first dose to death	Throughout study
Other	Assess gene expression	Profile gene expression in ctDNA	prior to PMD-026 administration
Other	Evaluate QT interval and PMD-026 concentrations	Qualitative and/or quantitative associations of PK parameter concentrations with QTcF changes	Throughout study
Primary	Safety and tolerability of PMD-026 in combination with fulvestrant in patients with HR+/HER2- previously treated breast cancer	Incidence of AEs, DLTs, SAEs. Changes in laboratory, vital signs, and ECG values.	6 weeks
Secondary	Plasma concentration of PMD-026 when administered in combination with fulvestrant	The plasma concentration will be measured as part of pharmacokinetic (PK) testing.	As determined by PK data
Secondary	Preliminary anti-tumor activity of PMD-026 when dosed in combination with fulvestrant	ORR, DOR, DCR, PFS	Until PD or death, up to 2 years