The purpose of this study is to find out whether tinengotinib in combination with abiraterone acetate and prednisone or enzalutamide is a safe treatment that causes few or mild side effects in people with metastatic castration-resistant prostate cancer (mCRPC).
Participants ≥ 18 years old, with signed informed consent
Histologically confirmed carcinoma of the prostate (neuroendocrine differentiation is allowed, but pure small cell carcinoma is not permitted)
Metastatic disease documented by at least 2 bone lesions on whole body radionuclide bone scan, or soft tissue disease documented by computed tomography (CT) scan/magnetic resonance imaging (MRI). Note: Metastatic disease seen only on PET imaging does not qualify.
Current ongoing therapy and observed tolerance with full standard dose of abiraterone acetate (1000 mg QD) or enzalutamide (160 mg QD) at the time of study entry. Enzalutamide or abiraterone acetate must have been started at least 90 days before screening assessments. An interruption of dosing of a maximum of 30 days is permitted prior to resuming the agent. Please note: Patients who are on a reduced dose or are intolerant of abiraterone acetate or enzalutamide at screening will not be eligible for study participation.
Pure small cell carcinoma
Previous exposure to multi-TKI therapies.
Uncontrolled hypertension (persistent systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg) or known coronary artery disease with angina. Patients with known hypertension must be on antihypertensive medication with BPs generally <140/90 to be eligible.
History of congestive heart failure of Class II-IV New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of study entry, or prolongation of QTc interval to >480 msec using Fridericia formula (QTcF) at screening (except for participants with pacemakers, where there is no QTc cutoff).
Sequential
Tinengotinib
DrugTinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily.
abiraterone acetate with prednisone
DrugAbiraterone acetate 1000 mg PO QD in combination with prednisone 5 mg PO once or twice daily (QD or BID)
Enzalutamide
DrugEnzalutamide 160 mg PO QD
RP2D
Evaluate DLT occurrence to confirm safety and RP2D
Objective Response Rate (ORR)
by local investigator's assessment per PCWG3-modified RECIST v1.1 in participants with baseline measurable disease OR rate of PSA decline of ≥ 50% from baseline in patients with a baseline PSA of 2.0 ng/mL or above
Rate of Radiographic Response (phase II)
Rate of radiographic response by local investigator's assessment per PCWG3-modified RECIST v1.1 in participants with baseline measurable disease
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Memorial Sloan Kettering Cancer Center
Lead sponsor
TransThera Sciences
Collaborator
