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

• ClinicalTrials.gov Identifier: NCT04556617
• Recruitment Status: Terminated
• First Posted: September 21, 2020
• Last Update Posted: October 5, 2022
• Sponsor: Opna-IO LLC
• Information provided by (Responsible Party): Opna-IO LLC

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: PLX2853; Drug: Olaparib; Drug: Abiraterone acetate; Drug: Prednisone	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: September 21, 2020
• Actual Primary Completion Date: May 24, 2022
• Actual Study Completion Date: May 24, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: PLX2853 + Abiraterone Acetate + Prednisone; Phase 1b (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 15 evaluable subjects with mCRPC will be enrolled. Phase 2a (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 19 evaluable subjects with mCRPC will be enrolled.	Drug: PLX2853; PLX2853 tablets; Drug: Abiraterone acetate; Abiraterone acetate tablets; Drug: Prednisone; Prednisone (or equivalent) tablets
Experimental: PLX2853 + Olaparib; Phase 1b (PLX2853 + Olaparib Combination): Up to 18 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled. Phase 2a (PLX2853 + Olaparib Combination): Up to 58 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled.	Drug: PLX2853; PLX2853 tablets; Drug: Olaparib; Olaparib tablets

Outcome Measures

Primary Outcome Measures :

1. Phase 2a (both arms): Disease response as defined by at least one of the following: Objective response by modified RECIST v1.1, PSA response, or circulating tumor cell count (CTC) response. [ Time Frame: 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. ]
2. Phase 1b (both arms): Incidence of dose-limiting-toxicities (DLTs) [ Time Frame: From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days). ]
3. Phase 1b (both arms): Incidence of TEAEs that are related to treatment [ Time Frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment. ]

Secondary Outcome Measures :

1. Radiographic progression-free survival (rPFS) (both arms, both phases) [ Time Frame: 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. ]
   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.
2. Time to PSA Progression (both arms, both phases) [ Time Frame: 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. ]
   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).
3. Duration of PSA Response (both arms, both phases) [ Time Frame: 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. ]
   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.
4. Overall Survival (OS) (both arms, both phases) [ Time Frame: From time of first dose until completion of long term follow-up, approximately 30 months. ]
   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.
5. Incidence of all TEAEs (both arms, both phases) [ Time Frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment. ]
6. Incidence of TEAEs that result in dose interruption, reduction or discontinuation (both arms, both phases) [ Time Frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment. ]
7. PLX2853 PK parameter AUC0-24 (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
   AUC from time zero extrapolated to 24 hours (AUC0-24)
8. PLX2853 PK parameter Cmax (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
   Maximum observed concentration
9. PLX2853 PK parameter T1/2 (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
   terminal elimination half-life (T1/2)
10. Best Overall Response (BOR) (both arms, both phases) [ Time Frame: 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. ]
    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.
11. Duration of Response (DOR) (both arms, both phases) [ Time Frame: 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 from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause.
12. Time to first Symptomatic Skeletal-Related Event (SSRE) (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]

    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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, South Carolina

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States, 29572

United States, Tennessee

Tennessee Oncology/ Sarah Cannon

Nashville, Tennessee, United States, 37203

United States, Virginia

Virginia Cancer Specialist

Fairfax, Virginia, United States, 22031

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

United Kingdom

Sarah Cannon Research Institute

London, United Kingdom, W1G 6AD

Sponsors and Collaborators

Opna-IO LLC

More Information

• Responsible Party: Opna-IO LLC
• ClinicalTrials.gov Identifier: NCT04556617
• Other Study ID Numbers: PLX124-04
• First Posted: September 21, 2020
• Last Update Posted: October 5, 2022
• Last Verified: October 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Opna-IO LLC:

PLX2853; Metastatic Castration-resistant Prostate Cancer; Olaparib; Abiraterone Acetate; Adenocarcinoma; Prostate Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Prednisone; Olaparib; Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors