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

NCT04115306

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/1b Study of Oral PMD-026 in Patients With Metastatic Breast Cancer and Metastatic 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

Clinical Trial IDs

  • ORG STUDY ID: PMD-026-1-001
  • NCT ID: NCT04115306

Conditions

  • Metastatic Breast Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
PMD-026PMD-026

Purpose

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.

Detailed Description

      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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
PMD-026ExperimentalOral PMD-026 (dose: 25 - 1000 mg), given daily until disease progression or unacceptable toxicity
  • PMD-026

Eligibility Criteria

        Inclusion Criteria:

          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:

               1. Absolute Neutrophil Count (ANC) ≥ 1500/mm^3

               2. Platelets ≥ 100,000/mm^3

               3. AST/SGOT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)

               4. ALT/SGPT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)

               5. Total bilirubin ≤ 1.5 x ULN (unless diagnosis of Gilbert's syndrome in which case
                  < 3.0 times ULN)

               6. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min

          9. If residual treatment related toxicity from prior therapy:

               1. Treatment related toxicity resolved to at least Grade 1 (alopecia excepted), or

               2. Treatment related toxicity resolved to at least Grade 2 with prior approval of
                  the Medical Monitor

         10. Available archival or fresh tumor tissue (Formalin-fixed paraffin-embedded [FFPE])

         11. [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

         12. [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

         13. [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

         14. [Females] If of childbearing potential, the patient must have a negative serum
             pregnancy test

        Exclusion Criteria:

          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:

               1. Congestive heart failure (NYHA classification ≥ 3 in within 6 months of first
                  dose of PMD-026

               2. Unstable angina pectoris

               3. Myocardial infarction within 12 months of study entry

               4. Arrhythmias requiring continued treatment (controlled atrial fibrillation
                  allowed)

               5. QTcF interval > 460 msec (using Fridericia's formula)

         18. 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)

         19. 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)

         20. 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

         21. Other known active cancer(s) likely to require treatment in the next year that would
             impact the assessment of any study endpoints

         22. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame:Through study completion, an average of 12 weeks
Safety Issue:
Description:Toxicities will be assessed in each patient by tracking the occurrence of graded Adverse Events (AEs). AEs will be graded according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v5.0.

Secondary Outcome Measures

Measure:Plasma Concentration
Time Frame:24 hours
Safety Issue:
Description:The plasma concentration will be measured as part of pharmacokinetic (PK) testing.
Measure:Time to Response
Time Frame:6 weeks
Safety Issue:
Description:The time to response will be evaluated by disease assessments.
Measure:Duration of Response
Time Frame:6 weeks
Safety Issue:
Description:The duration of response will be evaluated by disease assessments from time of first response (CR or PR) to time of disease progression.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Phoenix Molecular Designs

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