PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer

NCT04493619 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: PLX124-03
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 9

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.

Conditions

Gynecologic Neoplasms; Epithelial Ovarian Cancer

Keywords

PLX2853; Ovarian Cancer; ARID1A; Gynecological Malignancies; Carboplatin

Outcome Measures

Primary Outcomes (3)

• 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)

  Overall response rate as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  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.

• Phase 1b (PLX2853 + Carboplatin Combination): Establish the Number of Participants Reaching MTD/RP2D for the Combination of PLX2853 and Carboplatin

  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

  From time of first dose of PLX2853 and carboplatin until 30 days of end of treatment an average of 6 months.

• Phase 2a (PLX2853 + Carboplatin Combination): Number of Participants Reaching ORR as Measured by RECIST v1.1

  Overall response rate as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  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.

Study Arms (4)

Phase 2a PLX2853 Monotherapy (80 mg)

EXPERIMENTAL

Subjects with ARID1A mutation-positive advanced gynecological malignancies

Drug: PLX2853

Phase 1b PLX2853 (40 mg) + Carboplatin Combination Therapy

EXPERIMENTAL

Subjects with platinum-resistant EOC

Drug: PLX2853; Drug: Carboplatin

Phase 2a PLX2853 (80 mg) + Carboplatin Combination Therapy

EXPERIMENTAL

Subjects with platinum-resistant EOC

Drug: PLX2853; Drug: Carboplatin

Phase 1b PLX2853 (80 mg) + Carboplatin Combination Therapy

EXPERIMENTAL

Subjects with platinum-resistant EOC

Drug: PLX2853; Drug: Carboplatin

Interventions

PLX2853 DRUG

PLX2853 tablets

Phase 1b PLX2853 (40 mg) + Carboplatin Combination Therapy; Phase 1b PLX2853 (80 mg) + Carboplatin Combination Therapy; Phase 2a PLX2853 (80 mg) + Carboplatin Combination Therapy; Phase 2a PLX2853 Monotherapy (80 mg)

Carboplatin DRUG

Carboplatin IV injection, 5 mg•min/mL

Phase 1b PLX2853 (40 mg) + Carboplatin Combination Therapy; Phase 1b PLX2853 (80 mg) + Carboplatin Combination Therapy; Phase 2a PLX2853 (80 mg) + Carboplatin Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Non-healing wound, ulcer, or bone fracture
• Infection with HIV-1 or HIV-2. Exception: subjects with well-controlled HIV (e.g., CD4 \>350/mm3 and undetectable viral load) are eligible.
• 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 ribonucleic acid).
• 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

Sponsors & Collaborators

• Opna Bio LLC: lead

Study Sites (9)

The University of Chicago Medical Center

Chicago, Illinois, 05841, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Oklahoma - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology / Sarah Cannon

Nashville, Tennessee, 37203, United States

Location

University of Virginia Health Systems

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

University of Washington / Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Genital Neoplasms, Female; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Limitations and Caveats

This study was discontinued early due to a business decision by the sponsor. Only combined data were provided for the combo arm. No outcome measures were evaluated.

Results Point of Contact

• Title: Kerry Inokuchi
• Organization: Opna Bio

info@opnabio.com

650-204-4065

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 30, 2020
• Study Start: August 11, 2020
• Primary Completion: April 25, 2022
• Study Completion: April 25, 2022
• Last Updated: November 4, 2024
• Results First Posted: November 4, 2024

Record last verified: 2024-10

Locations

CA (1); US (8)