Clinical Trials /

A Study of PLX2853 in Advanced Malignancies.

NCT03297424

Description:

The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced malignancies.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Malignant Solid Tumor
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of PLX2853 in Advanced Malignancies.
  • Official Title: A Phase 1b/2a Dose-escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX2853 in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: PLX124-01
  • NCT ID: NCT03297424

Conditions

  • Small Cell Lung Cancer
  • Uveal Melanoma
  • Ovarian Clear Cell Carcinoma
  • Non-Hodgkin Lymphoma
  • Advanced Malignancies
  • Solid Tumor
  • Diffuse Large B Cell Lymphoma
  • Follicular Lymphoma

Interventions

DrugSynonymsArms
PLX2853PLX2853 tabletsPLX2853

Purpose

The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced malignancies.

Trial Arms

NameTypeDescriptionInterventions
PLX2853ExperimentalPhase 1b (Dose Escalation): Up to 30 Subjects with advanced malignancies. Phase 2a (Dose Expansion): There will be 5 total expansion cohorts. Either 10 or 29 subjects per cohort in each of 4 expansion cohorts: advanced SCLC, uveal melanoma, OCCC, and any other advanced malignancy with a known ARID1A mutation (between 40 to 116 subjects total for the solid tumor expansion phase). For the 5th expansion cohort, up to 20 subjects may be enrolled for NHL.
  • PLX2853

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of one of the following, and must be measurable or evaluable per
             RECIST 1.1 (solid tumors) or Lugano (NHL):

          -  Phase 1b:

               -  Histologically confirmed advanced refractory solid tumor that is measurable or
                  evaluable per RECIST 1.1 criteria.

               -  Histologically confirmed NHL: diffuse large B-cell lymphoma and follicular
                  lymphoma (Grade 1-3A) that has progressed following at least 1 line of prior
                  anticancer therapy.

          -  Phase 2a: Patients with various solid tumors or NHL who have received prior therapy.

          -  Age ≥18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          -  Life expectancy ≥3 months in the judgement of the investigator

          -  Adequate organ function as appropriate for the disease under study. All screening
             laboratory tests should be performed within 10 days of treatment initiation.

          -  Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at
             Screening (≤7 days prior to 1st study drug dose) and must agree to use an effective
             form of contraception from the time of the negative pregnancy test up to 6 months
             after the last dose of study drug. Effective forms of contraception include
             abstinence, hormonal contraceptive in conjunction with a barrier method, or a double
             barrier method. Women of non-child-bearing potential may be included if they are
             either surgically sterile or have been postmenopausal for ≥1 year.

          -  Fertile men must agree to use an effective method of birth control during the study
             and for up to 6 months after the last dose of study drug.

          -  All associated clinically significant drug-related toxicity from previous cancer
             therapy must be resolved prior to study treatment administration (alopecia is
             allowed).

          -  Willingness and ability to provide written informed consent prior to any study-related
             procedures and to comply with all study requirements

        Exclusion Criteria:

          -  Prior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610

          -  Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2

          -  Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

          -  Presence of symptomatic or uncontrolled central nervous system or leptomeningeal
             metastases

          -  Known or suspected allergy to the investigational agent or any agent given in
             association with this trial

          -  Clinically significant cardiac arrhythmias including bradyarrhythmias and/or subjects
             who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Subjects
             with controlled atrial fibrillation are not excluded.

          -  Inability to take oral medication or significant nausea and vomiting, malabsorption,
             or significant small bowel resection that, in the opinion of the Investigator, would
             preclude adequate absorption

          -  Non-healing wound, ulcer, or bone fracture

          -  Subject has known human immunodeficiency virus (HIV), hepatitis B or hepatitis C
             infection or is known to be a carrier of hepatitis B or C.

          -  History (within 2 years prior to first study drug administration) of another
             malignancy unless the malignancy was treated with curative intent and likelihood of
             relapse is small. Subjects with a history of squamous or basal cell carcinoma of the
             skin or carcinoma in situ of the cervix may be enrolled.

          -  Persistent, unresolved ≥Grade 2 clinically significant drug-related toxicity (except
             alopecia, erectile impotence, hot flashes, libido, neuropathy) associated with
             previous treatment

          -  Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1

          -  Receipt of anti-cancer therapy prior to Cycle 1 Day 1: no chemotherapy, radiation
             therapy, small molecule tyrosine kinase inhibitor (TKI), or hormonal therapy for the
             treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of Cycle 1
             Day 1. No immune therapy or other biologic therapy (other monoclonal antibodies or
             antibody-drug conjugates [ADCs]) for the treatment of cancer within 28 days of Cycle 1
             Day 1.

          -  Subject is receiving systemic steroids at doses greater than the equivalent of
             prednisone 10 mg daily, with the exception of intermittent use for the treatment of
             emesis

          -  Subject is participating in any other therapeutic clinical study (observational or
             registry trials are allowed)

          -  Female subjects who are pregnant or breast-feeding

          -  Presence of any other medical, psychological, familial, sociological, or geographic
             condition potentially hampering compliance with the study protocol or would interfere
             with the study endpoints or the subject's ability to participate in the study in the
             judgement of the investigator
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Time Frame:First dose of study drug through at least 30 days after end of treatment.
Safety Issue:
Description:The highest dose level at which less than 2 of 6 participants or less than 33% of participants (if cohort is expanded beyond 6) experience a dose limiting toxicity will be considered the maximum tolerated dose / recommended phase 2 dose.

Secondary Outcome Measures

Measure:Overall response rate (ORR) defined according to standard criteria for the relevant malignancy [Phase1b]
Time Frame:From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years.
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 2 years.
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:PFS time is defined as the time from the first dose of PLX2853 to disease progression or death, whichever occurs first, assessed up to 2 years.
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From the first dose of study drug until the date of death from any cause, assessed up to 2 years.
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Plexxikon

Trial Keywords

  • PLX2853
  • Small cell lung cancer (SCLC)
  • Uveal Melanoma
  • Ovarian Clear Cell Carcinoma
  • Non-Hodgkin Lymphoma
  • Advanced Malignancies
  • Solid Tumor
  • Diffuse Large B Cell Lymphoma (DLBCL)
  • Follicular Lymphoma (FL)
  • ARID1A

Last Updated

May 1, 2019