Clinical trial NCT04115306: Phase 1/1b/2 Study of Oral PMD-026 in Patients With Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Keywords: invasive breast cancer
PR-negative breast cancer
HER2-negative breast cancer
Breast cancer
Breast malignancy
breast malignancies
metastatic breast cancer
advanced breast cancer
solid tumor
late stage breast cancer/late-stage breast cancer
Lead sponsor: Phoenix Molecular Designs
Sponsor class: INDUSTRY
First posted: 2019-10-04
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Combination with fulvestrant (Part 3):

This study will prospectively 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.

Eligibility criteria: Inclusion Criteria, Combination with fulvestrant (Part 3):

* RSK2 positive from available archival or fresh tumor tissue (FFPE).
* Histologically or cytologically diagnosed HR+, HER2-
* 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):

* ≤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)

Primary outcomes:
measure: Safety and tolerability of PMD-026 in combination with fulvestrant in patients with HR+/HER2- previously treated breast cancer
timeFrame: 6 weeks
Secondary outcomes:
measure: Plasma concentration of PMD-026 when administered in combination with fulvestrant
timeFrame: As determined by PK data
measure: Preliminary anti-tumor activity of PMD-026 when dosed in combination with fulvestrant
timeFrame: Until PD or death, up to 2 years
Other outcomes:
measure: Assess OS
timeFrame: Throughout study
measure: Assess gene expression
timeFrame: prior to PMD-026 administration
measure: Evaluate QT interval and PMD-026 concentrations
timeFrame: Throughout study
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Farmington Hills
country: United States
facility: Profound Research
state: Michigan
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
Study officials:
References: