PLX2853 in Combination With Abiraterone Acetate and Predn... | NCT04556617

Label	Type	Description	Intervention Names
Phase 1b PLX2853 (20 mg) + Olaparib	Experimental	Phase 1b dose escalation	Drug: PLX2853 20 mg Drug: Olaparib
Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone	Experimental	Phase 1b dose escalation	Drug: Abiraterone acetate Drug: Prednisone Drug: PLX2853 40 mg
Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Experimental	Phase 1b dose escalation	Drug: Abiraterone acetate Drug: Prednisone Drug: PLX2853 80 mg
Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Experimental	Phase 2a dose expansion	Drug: Abiraterone acetate Drug: Prednisone Drug: PLX2853 80 mg
Phase 1b PLX2853 (40 mg) + Olaparib	Experimental	Phase 1b dose escalation	Drug: Olaparib Drug: PLX2853 40 mg

Name	Type	Description	Arm Group Labels	Other Names
PLX2853 20 mg	Drug	PLX2853 tablets	Phase 1b PLX2853 (20 mg) + Olaparib

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)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years at the time of signing informed consent.
Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
Eastern Cooperative Oncology Group Performance Status 0 to 1.
Adequate organ function as demonstrated following laboratory values.
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.
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).
Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

Exclusion Criteria:

Prior exposure to a bromodomain inhibitor.
History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
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.
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.
Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
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.
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.

Facility	Status	City	State	ZIP	Country	Contacts
University of Chicago		Chicago	Illinois	60637	United States
Karmanos Cancer Institute

ID	Title	Description
FG000	Phase 1b PLX2853 (20 mg) + Olaparib	Dose escalation Once daily dosing PLX2853 20 mg Twice daily dosing olap 300 mg
FG001	Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 29, 2021

ID	Title	Description
BG000	Phase 1b PLX2853 (20 mg) + Olaparib	Once daily dosing PLX2853 20 mg Twice daily dosing olap 300 mg
BG001	Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone	Once daily dosing of PLX2853 40 mg AA 1000 mg pred 10 mg
BG002	Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg
BG003	Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg
BG004	Phase 1b PLX2853 (40 mg) + Olaparib	Once daily dosing PLX2853 40 mg Twice daily dosing olap 300 mg
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG0001 BG0015 BG0027 BG0035 BG0041 BG00519

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Posted

Number

participants

From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days)

ID	Title	Description
OG000	Phase 1b PLX2853 (20 mg) + Olaparib	Dose escalation Once daily dosing PLX2853 20 mg Twice daily dosing olap 300 mg
OG001	Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone	Dose escalation Once daily dosing of PLX2853 40 mg AA 1000 mg pred 10 mg
OG002	Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Dose escalation Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg
OG003	Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Dose expansion Once daily dosing PLX2853 80 mg AA 1000 mg pred 10 mg
OG004	Phase 1b PLX2853 (40 mg) + Olaparib	Dose escalation Once daily dosing PLX2853 40 mg Twice daily dosing olap 300 mg

Units	Counts
Participants	OG0001 OG0015 OG0027 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

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.

Posted

Count of Participants

Participants

From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment (an average of 103 days)

ID	Title	Description
OG000	Phase 1b PLX2853 (20 mg) + Olaparib	Phase 1b dose escalation PLX2853 20 mg: PLX2853 tablets Olaparib: Olaparib tablets
OG001	Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone	Phase 1b dose escalation Abiraterone acetate: Abiraterone acetate tablets Prednisone: Prednisone (or equivalent) tablets PLX2853 40 mg: PLX2853 tablets
OG002	Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Phase 1b dose escalation Abiraterone acetate: Abiraterone acetate tablets Prednisone: Prednisone (or equivalent) tablets PLX2853 80 mg: PLX2853 tablets
OG003	Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Phase 2a dose expansion Abiraterone acetate: Abiraterone acetate tablets Prednisone: Prednisone (or equivalent) tablets PLX2853 80 mg: PLX2853 tablets

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.

Posted

Number

From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days)

ID	Title	Description
OG000	Phase 1b PLX2853 (20 mg) + Olaparib	Dose escalation Once daily dosing PLX2853 20 mg Twice daily dosing olap 300 mg
OG001	Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone	Dose escalation Once daily dosing of PLX2853 40 mg AA 1000 mg pred 10 mg
OG002	Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Dose escalation Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg
OG003	Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Dose expansion Once daily dosing PLX2853 80 mg AA 1000 mg pred 10 mg

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0011 events1 affected5 at risk EG0025 events5 affected7 at risk EG0030 events0 affected5 at risk EG0041 events1 affected1 at risk
pancytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
nausea	Gastrointestinal disorders	Systematic Assessment	EG0004 events1 affected1 at risk EG0014 events4 affected5 at risk EG0027 events7 affected7 at risk EG003
urinary tract infection	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0022 events2 affected7 at risk EG003
hypophosphatemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 events1 affected1 at risk EG0011 events1 affected5 at risk EG0022 events2 affected7 at risk EG003
pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
blurred vision	Eye disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0014 events4 affected5 at risk EG0022 events2 affected7 at risk EG003
dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
gastroesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0013 events3 affected5 at risk EG0020 events0 affected7 at risk EG003
dry heaving	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
fatigue	General disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0013 events3 affected5 at risk EG0026 events6 affected7 at risk EG003
unsteady gait	General disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
alanine aminotransferase increased	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
amylase increased	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
bilirubin increased	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
creatinine increased	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
elevated d-dimer	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
platelet count decreased	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected7 at risk EG003
weight loss	Investigations	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0026 events6 affected7 at risk EG003
hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
dizziness	Nervous system disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events2 affected7 at risk EG003
dysgeusia	Nervous system disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events2 affected7 at risk EG003
headache	Nervous system disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0012 events2 affected5 at risk EG0020 events0 affected7 at risk EG003
peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
tremors	Nervous system disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected7 at risk EG003
epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected7 at risk EG003
intermittent hyperhydrosis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG003
bloating	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
edema limbs	General disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
herpes simplex reactivation	Infections and infestations	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0024 events4 affected7 at risk EG003
low appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0022 events2 affected7 at risk EG003
dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0022 events2 affected7 at risk EG003
hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0024 events4 affected7 at risk EG003
acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
urinary tract obstruction	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
flatulence	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
chills	General disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
fever	General disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
shingles	Infections and infestations	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
dysuria	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
shortness of breath	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
itchy skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
skin rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
worsening hypertension	Vascular disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003

ID	Term
D000230	Adenocarcinoma
D011471	Prostatic Neoplasms

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1b PLX2853 (20 mg) + Olaparib	Once daily dosing PLX2853 20 mg Twice daily dosing olap 300 mg	1	1	1	1	1
EG001	Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + Prednisone	Once daily dosing of PLX2853 40 mg AA 1000 mg pred 10 mg	5	1	5	5	5
EG002	Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg	7	3	7	7	7
EG003	Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + Prednisone	Once daily dosing of PLX2853 80 mg AA 1000 mg pred 10 mg	5	2	5	5	5
EG004	Phase 1b PLX2853 (40 mg) + Olaparib	Once daily dosing PLX2853 40 mg Twice daily dosing olap 300 mg	1	0	1	1	1

Term	Organ System	Assessment Type	Statistical Information
Bone pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected7 at risk EG0030 events0 affected5 at risk EG0040 events0 affected1 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected7 at risk EG003
Blood bilirubin increase	Infections and infestations	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected7 at risk EG003

ID	Term
C531550	olaparib
D000069501	Abiraterone Acetate
D011241	Prednisone