A Multicenter, Open-Label, Parallel, Phase 2a Study of PLX2853 Monotherapy in Advanced Gynecological Malignancies With a Known ARID1A Mutation and Phase 1b/2a Study of PLX2853/Carboplatin Combination Therapy in Platinum-Resistant Epithelial Ovarian Cancer
Overview
- Phase
- Phase 1
- Intervention
- PLX2853
- Conditions
- Gynecologic Neoplasms
- Sponsor
- Opna Bio LLC
- Enrollment
- 37
- Locations
- 9
- Primary Endpoint
- Phase 2a (PLX2853 Monotherapy): Number of Participants With Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years at the time of signing informed consent
- •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).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
- •Adequate organ function as demonstrated by laboratory values.
- •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 year.
- •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).
- •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
- •Ongoing systemic infection requiring treatment with antibiotic, antiviral, or antifungal treatment
- •Autoimmune hemolytic anemia or autoimmune thrombocytopenia
- •Presence of symptomatic or uncontrolled central nervous system or leptomeningeal metastases
- •Red blood cell or platelet transfusion within 14 days of Screening blood draw
- •Known or suspected allergy to the investigational agent or any agent given in association with this study
- •Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 μg (NIH-ODS 2020).
- •Use of strong inhibitors and inducers of CYP3A4 and 2C8
- •Clinically significant cardiac disease
- •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
Arms & Interventions
Phase 2a PLX2853 Monotherapy (80 mg)
Subjects with ARID1A mutation-positive advanced gynecological malignancies
Intervention: PLX2853
Phase 1b PLX2853 (40 mg) + Carboplatin Combination Therapy
Subjects with platinum-resistant EOC
Intervention: PLX2853
Phase 1b PLX2853 (40 mg) + Carboplatin Combination Therapy
Subjects with platinum-resistant EOC
Intervention: Carboplatin
Phase 2a PLX2853 (80 mg) + Carboplatin Combination Therapy
Subjects with platinum-resistant EOC
Intervention: PLX2853
Phase 2a PLX2853 (80 mg) + Carboplatin Combination Therapy
Subjects with platinum-resistant EOC
Intervention: Carboplatin
Phase 1b PLX2853 (80 mg) + Carboplatin Combination Therapy
Subjects with platinum-resistant EOC
Intervention: PLX2853
Phase 1b PLX2853 (80 mg) + Carboplatin Combination Therapy
Subjects with platinum-resistant EOC
Intervention: Carboplatin
Outcomes
Primary Outcomes
Phase 2a (PLX2853 Monotherapy): Number of Participants With Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame: From 8 weeks of treatment for only PLX2853 (Cycle 3 Day 1; 28 days per cycle) until completion of long term follow-up, an average of 6 months.
Overall response rate as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Phase 1b (PLX2853 + Carboplatin Combination): Establish the Number of Participants Reaching MTD/RP2D for the Combination of PLX2853 and Carboplatin
Time Frame: From time of first dose of PLX2853 and carboplatin until 30 days of end of treatment an average of 6 months.
MTD is defined as the maximum tolerated dose, which is determined from dose-limiting toxicity. If DLTs are observed in 2 or more of 6 subjects (or ≥33% of the cohort) at a dose level, the dose at which this occurs will be considered intolerable and the MTD will have been exceeded. The MTD is the dose below the intolerable dose. RP2D is the recommended Phase 2 dose, which was determined to be 80 mg
Phase 2a (PLX2853 + Carboplatin Combination): Number of Participants Reaching ORR as Measured by RECIST v1.1
Time Frame: From 8 weeks of treatment with PLX2853 and Carboplatin (Cycle 3 Day 1; 28 days per cycle) until completion of long term follow-up, an average of 6 months.
Overall response rate as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)