PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination With Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Abiraterone acetate; Drug: Prednisone; Drug: Olaparib; Drug: PLX2853 20 mg; Drug: PLX2853 40 mg; Drug: PLX2853 80 mg

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology/ Sarah Cannon
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialist
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years at the time of signing informed consent.
2. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
3. Eastern Cooperative Oncology Group Performance Status 0 to 1.
4. Adequate organ function as demonstrated following laboratory values.
5. Fertile male subjects with female sexual partners must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of study drug.
6. Except as specified above for organ function, all drug-related toxicity from previous cancer therapy (including ongoing Abiraterone Acetate + Prednisone therapy if applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) 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.

Exclusion Criteria:

1. Prior exposure to a bromodomain inhibitor.
2. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
3. Clinically significant cardiac disease.
4. 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.

5. Active known second malignancy with the exception of any of the following:

   • Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin.
   • 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.
6. Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
7. 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 judgment of the Investigator.
8. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with less than protocol defined wash-out with the exception of Abiraterone Acetate (for subjects enrolling into Abiraterone Acetate Combination) and GnRH therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b PLX2853 (20 mg) + Olaparib; Phase 1b dose escalation	Drug: Olaparib; Olaparib tablets; Drug: PLX2853 20 mg; PLX2853 tablets
Experimental: Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone; Phase 1b dose escalation	Drug: Abiraterone acetate; Abiraterone acetate tablets; Drug: Prednisone; Prednisone (or equivalent) tablets; Drug: PLX2853 40 mg; PLX2853 tablets
Experimental: Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone; Phase 1b dose escalation	Drug: Abiraterone acetate; Abiraterone acetate tablets; Drug: Prednisone; Prednisone (or equivalent) tablets; Drug: PLX2853 80 mg; PLX2853 tablets
Experimental: Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone; Phase 2a dose expansion	Drug: Abiraterone acetate; Abiraterone acetate tablets; Drug: Prednisone; Prednisone (or equivalent) tablets; Drug: PLX2853 80 mg; PLX2853 tablets
Experimental: Phase 1b PLX2853 (40 mg) + Olaparib; Phase 1b dose escalation	Drug: Olaparib; Olaparib tablets; Drug: PLX2853 40 mg; PLX2853 tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-Limiting Toxicities	Dose limiting toxicity defined as clinically significant adverse events or laboratory abnormalities occurring during first cycle of study drug administration that are possibly related to study drug and that meet specific criteria defined in the protocol	From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days)
Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment	Treatment-emergent adverse events are those reported after study drug has been administered.	From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment (an average of 103 days)
Determination of Maximum Tolerated Dose	To be evaluated in both PLX2853 + AA + pred and PLX2853 + olap group; If DLTs observed in 2 or more subjects the dose will be considered intolerable and MTD will have been reached.	From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression-free survival (rPFS) (both arms, both phases)	Radiographic progression-free survival (PFS) will be calculated for each subject as the number of days from the first day of PLX2853 and combination agent(s) treatment (Cycle 1 Day 1) to the date of the first documented disease progression by either RECIST v.1.1 or on bone scan.	From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Time to PSA Progression (both arms, both phases)	PSA progression (defined per PCWG3 as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir, which is confirmed by a second consecutive value obtained 3 or more weeks later).	From 3 weeks of treatment (Cycle 2 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Duration of PSA Response (both arms, both phases)	Duration of PSA response will be calculated for each subject with a PSA response as the time from date of first documented, confirmed response (CR or PR) using PCWG3 until date of documented progression confirmed at least 3 weeks later, or death from any cause.	From 3 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Overall Survival (OS) (both arms, both phases)	Overall survival (OS) will be calculated for each subject as the number of days from the first day of PLX2853 treatment and combination agent(s) (Cycle 1 Day 1) to the date of death from any cause. If a subject is lost to follow-up, OS is censored at the date of last contact.	From time of first dose until completion of long term follow-up, approximately 30 months.
Incidence of all TEAEs (both arms, both phases)		From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment.
Incidence of TEAEs that result in dose interruption, reduction or discontinuation (both arms, both phases)		From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment.
PLX2853 PK parameter AUC0-24 (both arms, both phases)	AUC from time zero extrapolated to 24 hours (AUC0-24)	From time of first dose until 30 days from end of treatment.
PLX2853 PK parameter Cmax (both arms, both phases)	Maximum observed concentration	From time of first dose until 30 days from end of treatment.
PLX2853 PK parameter T1/2 (both arms, both phases)	terminal elimination half-life (T1/2)	From time of first dose until 30 days from end of treatment.
Best Overall Response (BOR) (both arms, both phases)	Best Overall Response (BOR) per RECIST v1.1 will be calculated for each subject with a minimum interval for confirmation of CR and PR of 4 weeks.	From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Duration of Response (DOR) (both arms, both phases)	Time from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause.	From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Time to first Symptomatic Skeletal-Related Event (SSRE) (both arms, both phases)	Time to first Symptomatic Skeletal-Related Event (SSRE) defined as: Use of radiation therapy to prevent or relieve skeletal symptoms.; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). Radiologic documentation is required.; Occurrence of spinal cord compression. Radiologic documentation required.; Orthopedic surgical intervention for bone metastasis.	From time of first dose until 30 days from end of treatment.

Collaborators and Investigators

• Sponsor: Opna Bio LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): May 24, 2022
• Study Completion (Actual): May 24, 2022

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Adenocarcinoma; Prostate Cancer; Olaparib; Abiraterone Acetate; Metastatic Castration-resistant Prostate Cancer; PLX2853
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Abiraterone Acetate; Prednisone; Olaparib
• Other Study ID Numbers: PLX124-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No