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

Opna Bio LLC

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Abiraterone acetate; Drug: Olaparib; Drug: PLX2853 40 mg; Drug: PLX2853 20 mg; Drug: PLX2853 80 mg; Drug: Prednisone

Study type: Interventional

Funder types: Industry

Identifiers

NCT04556617

PLX124-04

Details and patient eligibility

About

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)

Enrollment: 19 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 5 patient groups

Phase 1b PLX2853 (20 mg) + Olaparib

Experimental group

Description:

Phase 1b dose escalation

Treatment:

Drug: PLX2853 20 mg

Drug: Olaparib

Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone

Experimental group

Description:

Phase 1b dose escalation

Treatment:

Drug: Prednisone

Drug: PLX2853 40 mg

Drug: Abiraterone acetate

Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone

Experimental group

Description:

Phase 1b dose escalation

Treatment:

Drug: Prednisone

Drug: PLX2853 80 mg

Drug: Abiraterone acetate

Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone

Experimental group

Description:

Phase 2a dose expansion

Treatment:

Drug: Prednisone

Drug: PLX2853 80 mg

Drug: Abiraterone acetate

Phase 1b PLX2853 (40 mg) + Olaparib

Experimental group

Description:

Phase 1b dose escalation

Treatment:

Drug: PLX2853 40 mg

Drug: Olaparib