XL092 in Patients With Metastatic Castration-Resistant Prostate Cancer

Eligibility Criteria

• * Participant aged ≥ 18 years
• * Disease criteria:
• * Histologically or cytologically confirmed prostatic adenocarcinoma without small cell histology
• * Radiographic evidence of metatstatic disease
• * Progression on or after prior treatment with 177Lu-PSMA-617 as determined by clinical investigator
• * ECOG Performance Status ≤ 2.
• * Adequate organ function as defined as:
• * Platelet count ≥ 100,000/mm3 .
• * Hemoglobin ≥ 9 g/dL .
• * Total Bilirubin ≤ 1.5x institutional ULN. For subject's with Gilbert's disease, ≤ 3 x ULN.
• * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN. For subjects with CRPC and bone metastasis ALP ≤ 10 x ULN if predominantly bone-specific ALP.
• * International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 upper limit of normal (ULN)
• * Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault formula:
• * Urine protein-to-creatinine ratio (UPCR) ≤ 1.5 mg/mg (≤ 169.8 mg/mmol) creatinine or 24-hour urine protein \<1.5 g.
• * Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Section 5.4.1) during the course of the study and for 96 days after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm for the purpose of reproduction during these same periods.
• * Must have recovered from adverse effects of any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy). CTCAE adverse events less than or equal to grade 1 are acceptable. CTCAE adverse events grade 2 or greater may be acceptable as determined by the Clinical Investigator.
• * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• * Prior treatment with XL092
• * Receipt of any type of small molecule kinase inhibitor, cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks or at least 5 half-lives, whichever shorter before first dose of study treatment.
• * Radiation therapy for bone metastasis or any other radiation therapy within 2 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• * Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
• * (a) Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose low molecular weight heparins (LMWH) or prophylactic dose of specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban
• * (b) Therapeutic doses of LMWH or specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before enrollment and without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• * Cardiovascular disorders:
• * Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias \[eg, ventricular flutter, ventricular fibrillation, Torsades de pointes (TdP)\].
• * Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• * Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other clinically significant ischemic event within 6 months before first dose of study treatment.
• * Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA/TIA arterial thromboembolic events within 3 months before to first dose of study treatment.
• * Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• * Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• * Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta.
• * Other clinically significant disorders that would preclude safe study participation.
• * Active infection requiring systemic treatment. Note: Prophylactic antibiotic treatment is allowed.
• * Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• * Known positive test for or suspected infection with clinically significant SARS-CoV-2 within one month before enrollment. Note: demonstration that the subject has fully recovered from the infection as determined by clinical investigator is required to be eligible for enrollment
• * Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
• * Malabsorption syndrome.
• * Pharmacologically uncompensated, symptomatic hypothyroidism.
• * Moderate to severe hepatic impairment (Child-Pugh B or C).
• * Requirement for hemodialysis or peritoneal dialysis.
• * History of solid organ or allogeneic stem cell transplant.
• * Major surgery (as defined in Appendix B; eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic nephrectomy within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.
• * History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
• * Inability to swallow tablets.
• * Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• * Any other active malignancy or diagnosis of another malignancy within 2 years before first dose of study treatment requiring systemic treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
• * Other conditions, which in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study.
• * Participants taking prohibited medications as described in Section 6.8. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.