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. 2025 Sep 18;35(6):696–706. doi: 10.1097/MOU.0000000000001341

Table 1.

Toxicity of different new drugs targeting the androgen receptor pathway

Mechanism of action Drug Specificity Design PMID n Population Associated drug (excepted ADT) Primary endpoint DLT/MTD SAE and/or grade ≥ 3 toxicity Frequency (%) AE classification DDI
Androgen biosynthesis inhibitors ODM-208 CYP11A1 inhibitor phase 1 38320513 47 mCRPC post ARPI and post chemo 0 safety; define DMT 1 DLT (adrenal insufficiency): 50 mg BID adrenal insufficiency 31.9 NCI CTCAE (v4.03) 0
anemia 14.9
hyponatremia 12.8
hypertension 10.6
pulmonary embolism 10.6
tumor pain 8.5
amylase increased 8.5
lipase increased 6.4
ALP increased 6.4
CPK increased 4.3
asthenia 4.3
ALT/AST increased 2.1
hyperkaliemia 2.1
bone pain 2.1
diarrhea 2.1
abdominal pain 2.1
constipation 2.1
hypokalemia 2.1
phase 2 45 mCRPC post ARPI and post chemo; with AR mutation 0 safety; preliminary efficacy NA anemia 13.3
adrenal insufficiency 6.7
hypertension 6.7
pulmonary embolism 6.7
tumor pain 6.7
ALP increased 6.7
fatigue 6.7
asthenia 4.4
bone pain 4.4
diarrhea 4.4
dyspnea 4.4
back pain 4.4
hypotension 4.4
hyponatremia 4.4
amylase increased 2.2
lipase increased 2.2
hyperkaliemia 2.2
hyperkaliemia 2.2
muscle spasms 2.2
arthralgia 2.2
decreased appetite 2.2
urinary tract infection 2.2
Galeterone CYP 17 inhibitor, AR antagonist and AR degrader phase 1 26527750 49 m0CRPC or mCRPC; chemo and ARPI naive 0 safety; define DMT and RP2D Not reported ALT increased 16.3 NCI CTCAE (v4.0) 0
AST increased 6.1
bilirubin increased 2
fatigue 2
phase 2 28 m0CRPC or mCRPC chemo and enza-naive (abiretone authorized) 0 pharmacokinetic; safety and efficacy No DLT observed ALT increased 10.7
AST increased 3.6
constipation 3.6
diarrhea 3.6
rash 3.6
phase 3 31542304 19 mCRPC chemo and ARPI naive; AR-V7 + 0 screen and characterize AR-V7+ mCRPC, efficacy NA anemia 11 not reported 0
fatigue 5
hepatic failure 5
Novel AR antagonist HC-1119 deuterated form of enzalutamide phase 1 (dose escalation) 34109624 24 mCRPC ARPI naive (post chemo authorized) 0 safety, PK, DLT and PD No DLT observed; MTD not reached hypertension 6 NCI CTCAE (v4.03) 0
anemia 6
phase 1 (dose expansion) 19 0 PSA response Not reported hypertension 5
neutropenia 5
proteinuria 5
SHR3680 AR antagonist with low brain distribution phase 1/2 35241087 197 mCRPC post chemo; ARPI naive 0 phase 1: safety. Phase 2: PSA response rate No DLT observed; MTD not reached leucopenia 1.5 NCI CTCAE (v4.03) 0
neutrophil count decreased 1
hypertension 1
hypertriglyceridemia 0.5
decreased appetite 0.5
elevated ALT 0.5
gynecomastia 0.5
anemia 0.5
GT0918 = proxalutamide AR antagonist with higher affinity than enzalutamide phase 1 32460179 16 mCRPC post chemo +/- post ARPI 0 safety, PK and anti tumor efficacy No DLT observed; MTD not reached 0 not reported NCI CTCAE (v4.0) 0
phase 2 36919366 108 mCRPC ARPI naive (post chemo authorized) 0 PSA response rate NA anemia 2.8 NCI CTCAE (v4.0) 0
decreased appetite 1.9
fatigue 1.9
hypertension 1.9
weight loss 0.9
hypertriglyceridemia 0.9
hypokalemia 0.9
hypophosphatemia 0.9
elevated ALT 0.9
decreased neutrocyte 0.9
supraventricular extrasystole 0.9
hypotension 0.9
TAS3681 AR and AR-SV antagonist phase 1 NCT02566772a 56 mCRPC post ARPI and post chemo 0 DLT and safety 3 DLT (prolonged QTc and hypertension) at 600 mg QD and 400 mg BID not reported 21.4 NCI CTCAE (v4.0) not reported
AR PROTAC degrader BMS-986365

(CC-94676)		 dual effect (AR degrader and AR antagonist) phase 1 39293515 part A (dose escalation): 27 mCRPC post ARPI and post chemo 0 safety; define MTD and/or RP2D MTD not reached. 1 DLT (prolonged QTc): 900 mg BID prolonged QTc 14 NCI CTCAE (v5.0) antiarrhythmic drugs that prolong the QT were an exclusion criteria
part B (dose expansion): 68 NA prolonged QTc 9
bradycardia 3
syncope 1
hypertension 1
dyspnea and general oedema 1
Bavdegalutamide = ARV110 phase 1 NCT03888612b 18 mCRPC post ARPI +/- post chemo 0 MTD and RP2D 1 DLT (elevated ALT/AST and acute renal failure) at 280 QD twice daily AST/ALT elevation 11 NCI CTCAE (v5.0) Rosuvastatin
phase 1/2 NCT03888612c 153 mCRPC post ARPI +/- post chemo 0 efficacy (ORR) NA anemia 5 NCI CTCAE (v5.0) not reported
diarrhea 2
fatigue 1
vomiting 1
nausea 1
AST elevation 1
ARV-766 phase 1/2 NCT05067140d 103 mCRPC post ARPI +/- post chemo 0 safety (phase 1); clinical activity (phase 2) No DLT observed; MTD not reached fatigue 3 NCI CTCAE (v5.0) not reported
nausea 1
diarrhea 1
HP518 phase 1 NCT05252364e 22 mCRPC post ARPI and ≤ 1 line of chemo 0 safety and RP2D No DLT observed not reported NCI CTCAE (v5.0) not reported
AR-V inhibitor Niclosamide AR-V inhibitor, and Pi3K/AKT/mTOR, NF-κB, and Wnt-signaling inhibitor phase 1 29856824 5 mCRPC post ARPI Enzalutamide safety MTD = 500 mg TID. 2 DLT (nausea, vomiting, diarrhea and colitis) at 1000 mg TID nausea 20 NCI CTCAE (v4.0) not reported
vomiting 20
diarrhea 40
colitis 20
abdominal pain 20
Niclosamide reformulated (PDMX1001) phase 1b 33737681 9 mCRPC abiraterone naive (post enzalutamide and/or chemo authorized) Abiraterone MTD and RP2D No DLT observed fatigue 11 NCI CTCAE (v4.0) not reported
abdominal pain 11
hypoalbuminemia 11
anemia 11
hyperglycemia 11
AR-NTD inhibitor (anitens) EPI-506 phase 1 34843005 28 mCRPC post ARPI +/- post chemo 0 safety MTD not reached. 6 DLT observed in 4 patients (at 640 mg; 1800 mg BID; 3600 mg QD and 3600 mg QD) elevated amylase 4 NCI CTCAE (v4.03) not reported
abdominal pain 4
elevated ALT 4
elevated AST 4
nausea 4
vomiting 4
Masofaniten (EPI-7386) phase 1 NCT05075577f 18 mCRPC ARPI naive (post chemo authorized) Enzalutamide safety Not reported rash 6 NCI CTCAE (v5.0) not reported
hypertension 6
back pain 6

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