Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
PLX2853, Metastatic Castration-resistant Prostate Cancer, Olaparib, Abiraterone Acetate, Adenocarcinoma, Prostate Cancer
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)
Interventions
DRUGPLX2853 20 mg
PLX2853 tablets
DRUGOlaparib
Olaparib tablets
DRUGAbiraterone acetate
Abiraterone acetate tablets
DRUGPrednisone
Prednisone (or equivalent) tablets
DRUGPLX2853 40 mg
PLX2853 tablets
DRUGPLX2853 80 mg
PLX2853 tablets
Sponsors
Opna Bio LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities | From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days) | 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 |
| Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment | From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment (an average of 103 days) | Treatment-emergent adverse events are those reported after study drug has been administered. |
| Determination of Maximum Tolerated Dose | From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days) | 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. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b PLX2853 (20 mg) + Olaparib Once daily dosing PLX2853 20 mg
Twice daily dosing olap 300 mg | 1 |
| Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone Once daily dosing of PLX2853 40 mg AA 1000 mg pred 10 mg | 5 |
| Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg | 7 |
| Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg | 5 |
| Phase 1b PLX2853 (40 mg) + Olaparib Once daily dosing PLX2853 40 mg
Twice daily dosing olap 300 mg | 1 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 3 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 2 | 0 | 0 |
| Overall Study | progressive disease | 0 | 2 | 2 | 1 | 1 |
| Overall Study | PSA increase | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor study termination | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Phase 1b PLX2853 (40 mg) + Olaparib | Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone | Phase 1b PLX2853 (20 mg) + Olaparib |
|---|---|---|---|---|---|---|
| Age, Continuous | 68.3 years | 73 years | 68.2 years | 68.9 years | 66.4 years | 69 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 19 participants | 1 participants | 5 participants | 7 participants | 5 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 19 Participants | 1 Participants | 5 Participants | 7 Participants | 5 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 5 | 0 / 7 | 0 / 5 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 5 / 5 | 7 / 7 | 5 / 5 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 1 / 5 | 3 / 7 | 2 / 5 | 0 / 1 |
Outcome results
Primary
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.
Time frame: From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b PLX2853 (20 mg) + Olaparib | Determination of Maximum Tolerated Dose | NA mg |
| Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone | Determination of Maximum Tolerated Dose | NA mg |
| Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Determination of Maximum Tolerated Dose | NA mg |
| Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Determination of Maximum Tolerated Dose | NA mg |
| Phase 1b PLX2853 (40 mg) + Olaparib | Determination of Maximum Tolerated Dose | NA mg |
Primary
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
Time frame: From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b PLX2853 (20 mg) + Olaparib | Number of Participants With Dose-Limiting Toxicities | 0 participants |
| Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone | Number of Participants With Dose-Limiting Toxicities | 0 participants |
| Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Number of Participants With Dose-Limiting Toxicities | 0 participants |
| Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Number of Participants With Dose-Limiting Toxicities | 0 participants |
| Phase 1b PLX2853 (40 mg) + Olaparib | Number of Participants With Dose-Limiting Toxicities | 0 participants |
Primary
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.
Time frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment (an average of 103 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b PLX2853 (20 mg) + Olaparib | Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment | 1 Participants |
| Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone | Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment | 5 Participants |
| Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment | 7 Participants |
| Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone | Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment | 5 Participants |
| Phase 1b PLX2853 (40 mg) + Olaparib | Phase 1b (Both Arms): Incidence of TEAEs That Are Related to Treatment | 1 Participants |