The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics
and preliminary efficacy of the investigational drug PLX2853 in Advanced Gynecological
Malignancies with a Known ARID1A Mutation and PLX2853/Carboplatin Combination Therapy in
Platinum-Resistant Epithelial Ovarian Cancer.
1. Age ≥18 years at the time of signing informed consent
2. Histologically or cytologically confirmed diagnosis of 1 of the following, and must
have measurable disease per RECIST v1.1:
- Phase 2a (PLX2853 monotherapy): Any advanced gynecological malignancy (cervical,
vaginal, vulvar, uterine, ovarian, fallopian tube, or primary peritoneal) with a
known ARID1A mutation, that is intolerant to or refractory to all standard
therapy known to confer clinical benefit.
- Phase 1b and Phase 2a (PLX2853 + carboplatin combination):
Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer).
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
4. Adequate organ function as demonstrated by laboratory values.
5. Women of child bearing potential (defined as any female who has experienced menarche
and who has not undergone successful surgical sterilization or is not postmenopausal)
must have a negative serum pregnancy test within 7 days prior to taking the first dose
of study drug and, if sexually active, must agree to use a highly effective method of
contraception (a contraception method with a failure rate <1% per year) and 1
additional barrier method from the time of the negative pregnancy test to 90 days
after the last dose of study drug. Women of non-child bearing potential may be
included if they are either surgically sterile or have been postmenopausal for ≥1
6. Except as specified above for organ function, all drug-related toxicity from previous
cancer therapy must be resolved (to Grade ≤1 or baseline per National Cancer Institute
Common Terminology Criteria for Adverse Events version 5.0 [NCI CTCAE v5.0]) prior to
study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or
neuropathy is allowed).
7. Willingness and ability to provide written informed consent prior to any study-related
procedures and to comply with all study requirements
1. Prior exposure to a bromodomain inhibitor
2. Ongoing systemic infection requiring treatment with antibiotic, antiviral, or
3. Autoimmune hemolytic anemia or autoimmune thrombocytopenia
4. Presence of symptomatic or uncontrolled central nervous system or leptomeningeal
5. Red blood cell or platelet transfusion within 14 days of Screening blood draw
6. Known or suspected allergy to the investigational agent or any agent given in
association with this study
7. Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the
daily adequate intake of 30 μg (NIH-ODS 2020).
8. Use of strong inhibitors and inducers of CYP3A4 and 2C8
9. Clinically significant cardiac disease
10. 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
11. Non-healing wound, ulcer, or bone fracture
12. Infection with HIV-1 or HIV-2. Exception: subjects with well-controlled HIV (e.g., CD4
>350/mm3 and undetectable viral load) are eligible.
13. Current active liver disease from any cause, including hepatitis A (hepatitis A virus
immunoglobulin M positive), hepatitis B (hepatitis B virus [HBV] surface antigen
positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV
14. Active known second malignancy with the exception of any of the following:
- Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or
in situ cervical cancer
- Adequately treated Stage I cancer from which the subject is currently in
remission and has been in remission for ≥2 years
- Any other cancer from which the subject has been disease-free for ≥3 years
15. Major surgery or significant traumatic injury within 28 days prior to Cycle 1 Day 1
16. Hospitalization for subacute bowel obstruction within 28 days prior to Cycle 1 Day 1
17. Receipt of anti-cancer therapy prior to Cycle 1 Day 1:
- Chemotherapy, radiation therapy, or small molecule anti-cancer therapy for the
treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of
Cycle 1 Day 1
- Immune therapy or other biologic therapy (e.g., monoclonal antibodies,
antibody-drug conjugates) for the treatment of cancer within 21 days or 5
half-lives (whichever is shorter) of Cycle 1 Day 1 Subjects can receive a stable
dose of bisphosphonates for bone metastases, before and during the study as long
as these were started at least 28 days prior to treatment with study drug.
18. Subject is participating in any other therapeutic clinical study (observational or
registry studies are allowed).
19. Subjects who are pregnant or breast-feeding
20. 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.