PRIMARY OBJECTIVE:
I. To evaluate efficacy of erdafitinib in subjects with advanced prostate cancer who have
progressed on a second-generation androgen receptor (AR)-targeting agents (SART).
SECONDARY OBJECTIVES:
I. To evaluate the objective response rate. II. To measure time on treatment (ToT) as a
surrogate of clinical efficacy and progression-free survival (PFS).
III. To measure PFS. IV. To correlate bone specific alkaline phosphatase (BAP) modulation
with response and ToT.
V. To correlate prostate specific antigen (PSA) modulation with response and ToT.
VI. To characterize the safety profile of subjects treated with erdafitinib. VII. To measure
overall survival. VIII. To collect and archive bone marrow biopsies and aspirates, serum and
plasma in study patients for later hypothesis generating associations.
EXPLORATORY OBJECTIVE:
I. To evaluate DNA, ribonucleic acid (RNA), or protein biomarkers in tissue and blood samples
which potentially predict tumor response or resistance to erdafitinib.
OUTLINE:
Patients receive erdafitinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21
days in the absence of disease progression or unacceptable toxicity. Patients may also
undergo collection of blood and bone marrow via biopsy and aspirates.
After completion of study treatment, patients are followed up at 30 days, every 16 weeks for
1 year, and then every 6 months thereafter.
Inclusion Criteria:
- Age >= 18 years
- Histologically proven adenocarcinoma or small cell of the prostate with evidence for
skeletal metastases on bone scan and/or computed tomography (CT)/positron emission
tomography (PET)/magnetic resonance imaging (MRI) scan. Eastern Cooperative Oncology
Group (ECOG) performance status =< 2
- Serum testosterone levels =< 50 ng/ml and maintenance of castration with luteinizing
hormone-releasing hormone (LHRH) agonist/antagonist or orchiectomy
- Patients must have documented evidence of progressive disease as defined by any of the
following:
- PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum
of 7 days apart with the last result being at least >= 1.0 ng/mL
- New or increasing non-bone disease (Response Evaluation Criteria in Solid Tumors
[RECIST] 1.1 criteria)
- Positive bone scan with 2 or more new lesions (Prostate Cancer Working Group 3
[PCWG3])
- Prior treatment with a second-generation AR-targeting agent (e.g. abiraterone acetate,
enzalutamide, apalutamide) is required. Patients may have received up to two such
agents
- Patients may have received prior treatment with immunotherapies (sipuleucel-T,
checkpoint immunotherapies) or bone targeting therapies (radium-223)
- Both chemotherapy-naive and patients previously treated with chemotherapy are
eligible. Chemotherapy pretreated patients may have received a maximum of two prior
systemic cytotoxic chemotherapies completed at least 3 weeks prior to initiation of
study treatment
- Hemoglobin >= 8.0 g/dL
- Platelet count >= 75,000/uL
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Calculated creatinine clearance (Cockcroft-Gault Equation) >= 40 mL/min
- Serum potassium >= institutional lower limit of normal (ILLN)
- Serum magnesium >= ILLN
- Serum albumin >= 3.0 g/dL
- Serum bilirubin < 1.5 x institutional upper limit of normal (IULN) (except for
patients with known Gilbert's disease)
- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN
for patients without liver metastases. For patients with liver metastases AST or ALT <
5 x IULN is allowed
- Able to swallow study drugs whole as a tablet/capsule
- Patients must agree to tissue and blood collection for correlative studies at the
specified time points
- Male subject with a female partner of childbearing potential or pregnant must agree to
use two acceptable methods of contraception and not to donate sperm from time of
screening until 3 months after the last dose of study treatments
Exclusion Criteria:
- Radiation therapy to primary tumor or metastatic sites within 2 weeks of cycle 1, day
1
- Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 30 days prior to randomization
- A malignancy (other than the one treated in this study) which required radiotherapy or
systemic treatment within the past 1 year, or has a >= 30% probability of recurrence
within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)
- Chronically uncontrolled hypertension, defined conventionally as consistent systolic
pressures above 160 or diastolic pressures above 100 despite anti-hypertensive
therapy. Note that this is NOT a criterion related to particular blood pressure (BP)
results at the time of assessment for eligibility, nor does it apply to acute BP
excursions that are related to iatrogenic causes, acute pain or other transient,
reversible causes. (For example doctor's visit related stress i.e. "white coat
syndrome")
- Eye conditions likely to increase the risk of eye toxicity including
- Corneal or retinal abnormality likely to increase the risk of eye toxicity, or
lens conditions such as: untreated mature or hypermature senile cataract,
affecting visual acuity that impair the ability to interpret the Amsler grid test
- History of central serous retinopathy (CSR) or retinal vascular occlusion (RVO)
- Active wet, age-related macular degeneration (AMD)
- Diabetic retinopathy with macular edema (non-proliferative)
- Uncontrolled glaucoma (per local standard of care)
- Corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal
abrasion, inflammation or ulceration
- Any underlying medical or psychiatric condition, which in the opinion of the
investigator, will make the administration of study drug hazardous or obscure the
interpretation of adverse events
- History of uncontrolled cardiovascular disease including:
- Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de
Pointes, cardiac arrest, or known congestive heart failure class III-V within the
preceding 3 months; cerebrovascular accident or transient ischemic attack within
the preceding 3 months
- Mobitz II second degree heart block or third degree heart block
- Corrected QT interval (QTc) prolongation as confirmed by triplicate assessment at
screening (Fridericia; QTc > 480 milliseconds)
- Pulmonary embolism or other venous thromboembolism (VTE) within the preceding 2
months
- Known active autoimmune deficiency syndrome (AIDS) (human immunodeficiency virus [HIV]
infection), unless the subject has been on a stable anti-retroviral therapy regimen
for the last 6 months or more, has had no opportunistic infections in the last 6
months, and has CD4 count > 350
- Known active hepatitis B or C infection (subjects with history of hepatitis C
infection but negative hepatitis C virus polymerase chain reaction ([PCR] test and
subjects with hepatitis B with positive hepatitis B surface antibody are allowed)
- Not recovered from reversible toxicity of prior anticancer therapy (except toxicities
which are not clinically significant such as alopecia, skin discoloration, grade 1
neuropathy, grade 1-2 hearing loss)
- Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers,
known gastric ulcers, or unhealed incisions
- Major surgery within 4 weeks before randomization
- Untreated symptomatic spinal cord compression
