The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics
and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced
- 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
- 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
- Willingness and ability to provide written informed consent prior to any study-related
procedures and to comply with all study requirements
- 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
- 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
- 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
- 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
- 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