Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA UCSD
Dates
study started
estimated completion

Description

Summary

The purpose of this study is to test the safety and tolerability of PMD-026 in patients with metastatic breast cancer and triple negative breast cancer. PMD-026 is a targeted oral agent designed to kill tumor cells in metastatic breast cancer and triple negative breast cancer.

Official Title

Phase 1/1b Multicenter, Open-Label, First-in-Human Dose Escalation and Dose Expansion Study to Assess Safety and Tolerability of Orally Administered PMD-026 in Patients With Metastatic Breast Cancer With Expansion in Metastatic Triple Negative Breast Cancer

Details

This study will evaluate the safety and tolerability of PMD-026 using an accelerated titration design to define the MTD in metastatic breast cancer, followed by an expansion at the RP2D in triple negative breast cancer. All patients will receive daily oral doses of PMD-026 until either disease progression or unacceptable toxicity. Patients will have disease assessments initially after 6 weeks of treatment, and every 9 weeks thereafter. Patients enrolled to the Dose Escalation Phase must have histologically or cytologically diagnosed metastatic breast cancer that has progressed on or after standard of care therapy. Patients enrolled to the Dose Expansion Phase must have histologically or cytologically diagnosed metastatic triple negative breast cancer that has progressed on or after standard of care therapy. All patients must provide tumor tissue (archival preferred) prior to study entry. A subset (N=12) of patients in Part 2 of the study will participate in a 1- week evaluation of the effect of food on PMD-026 oral absorption. PMD-026 is an oral, reversible small molecule inhibitor of RSK1-4 with high selectivity for RSK2. High levels of RSK2 expression have been associated with worse overall survival in breast cancer. Inhibiting RSK2 may inhibit growth of breast cancer.

Keywords

Metastatic Breast Cancer Triple Negative Breast Cancer invasive breast cancer ER-negative breast cancer PR-negative breast cancer HER2-negative breast cancer Triple-Negative Breast Cancer TNBC Breast cancer Breast malignancy breast malignancies Metastatic TNBC Metastatic Triple-Negative Breast Cancer Metastatic Triple Negative Breast Cancer advanced breast cancer solid tumor late stage breast cancer/late-stage breast cancer Breast Neoplasms Triple Negative Breast Neoplasms PMD-026

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Signed informed consent
  2. Age ≥ 18 years
  3. ECOG Performance Status ≤ 2
  4. [Part 1 - Dose Escalation] Histologically or cytologically diagnosed metastatic breast cancer that has progressed on or after standard of care therapy and for which no standard of care therapy is available that would confer clinical benefit
  5. [Part 2 - Dose Expansion] Histologically or cytologically diagnosed metastatic triple-negative breast cancer that has progressed on or after standard of care therapy and for which no standard of care therapy is available that would confer clinical benefit
  6. [Part 1 - Dose Escalation] Evaluable or measurable disease by RECISTv1.1
  7. [Part 2 - Dose Expansion] Measurable disease by RECISTv1.1
  8. Adequate laboratory parameters including:
  9. Absolute Neutrophil Count (ANC) ≥ 1500/mm3

  10. Platelets ≥ 100,000/mm3

  11. AST/SGOT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
  12. ALT/SGPT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
  13. Total bilirubin ≤ 1.5 x ULN (unless diagnosis of Gilbert's syndrome in which case < 3.0 times ULN)
  14. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min
  15. If residual treatment related toxicity from prior therapy:
  16. Treatment related toxicity resolved to at least Grade 1 (alopecia excepted), or
  17. Treatment related toxicity resolved to at least Grade 2 with prior approval of the Medical Monitor
  18. . Available archival or fresh tumor tissue (Formalin-fixed paraffin-embedded [FFPE])
  19. . [Females] The patient must be postmenopausal, surgically sterile, or agree to use adequate contraception (adequate as determined by the PI - may include abstinence) throughout the study and for a least 30 days following the last dose of PMD-026
  20. . [Males] The patient must be surgically sterile or must agree to use adequate contraception (adequate as determined by the PI - may include abstinence) throughout the study and for at least 30 days following the last dose of PMD-026
  21. . [Males] The patient must agree to refrain from donating sperm throughout the study and for at least 30 days following the last dose of PMD-026
  22. . [Females] If of childbearing potential, the patient must have a negative serum pregnancy test

You CAN'T join if...

  1. ≤ 14 days from prior chemotherapy, biological or investigational therapy
  2. Use of any medications known to result in a prolongation of the QT/QTc interval
  3. Use of any medication that is a strong inducer or substrate of cytochrome P450 3A
  4. Use of any medications that is a substrate of BCRP
  5. Use of any medication that is a substrate of MATE2K
  6. ≤ 28 days from prior irradiation (including therapeutic radioisotopes such as strontium 89)
  7. ≤ 7 days from limited field irradiation for palliation
  8. ≤ 28 days from major surgical procedures
  9. ≤ 7 days from minor surgical procedures (no waiting period required following central catheter placement)
  10. . Central nervous system metastases, unless appropriately treated and neurologically stable for ≥ 28 days
  11. . Known history of leptomeningeal metastases
  12. . Uncontrolled bacterial, viral, or fungal infection (s) requiring systemic therapy
  13. . Pregnant or currently breast-feeding
  14. . Known Hepatitis B or Hepatitis C infection
  15. . Known HIV-positive with CD4+ cell counts < 350 cells/uL
  16. . Known HIV-positive with a history of an AIDS-defining opportunistic infection
  17. . History of clinically significant cardiovascular abnormalities including:
  18. Congestive heart failure (NYHA classification ≥ 3 in within 6 months of first dose of PMD-026
  19. Unstable angina pectoris
  20. Myocardial infarction within 12 months of study entry
  21. Arrhythmias requiring continued treatment (controlled atrial fibrillation allowed)
  22. QTcF interval > 460 msec (using Fridericia's formula)
  23. . Presence of active gastrointestinal disease or other condition that is expected to interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥ 2, and malabsorption syndrome)
  24. . Inadequately controlled hypertension defined as systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg (patients with values above these levels must have their blood pressure controlled prior to starting treatment)
  25. . Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment
  26. . Other known active cancer(s) likely to require treatment in the next year that would impact the assessment of any study endpoints
  27. . Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

Locations

  • University of California, Los Angeles (UCLA) accepting new patients
    Los Angeles California 90095 United States
  • University of California, San Diego (UCSD) accepting new patients
    San Diego California 92093 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Phoenix Molecular Designs
ID
NCT04115306
Phase
Phase 1
Study Type
Interventional
Last Updated