Metastatic Breast Cancer
Conditions
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
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 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.
Interventions
DRUGPMD-026
Investigational Drug
DRUGfulvestrant
SERDs
Sponsors
Phoenix Molecular Designs
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of PMD-026 in combination with fulvestrant in patients with HR+/HER2- previously treated breast cancer | 6 weeks | Incidence of AEs, DLTs, SAEs. Changes in laboratory, vital signs, and ECG values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of PMD-026 when administered in combination with fulvestrant | As determined by PK data | The plasma concentration will be measured as part of pharmacokinetic (PK) testing. |
| Preliminary anti-tumor activity of PMD-026 when dosed in combination with fulvestrant | Until PD or death, up to 2 years | ORR, DOR, DCR, PFS |
Countries
United States
Outcome results
None listed