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

Phoenix Molecular Designs

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Metastatic Breast Cancer

Treatments

Drug: fulvestrant

Drug: PMD-026

Study type

Interventional

Funder types

Industry

Identifiers

NCT04115306

PMD-026-1-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

61 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)