A Phase Ib Dose-Escalation Study of Cabozantinib in Combination With Lutetium-177 (177Lu)-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
This is an open-label, phase 1b dose-escalation study of cabozantinib in combination with 177Lu-PSMA-617 in subjects with mCRPC. The primary hypothesis is that cabozantinib with 177Lu-PSMA will be safe and have efficacy in patients with mCRPC. The dose-escalation phase (Part 1) will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule for the subsequent expansion phase (Part 2).
• Male subject aged ≥ 18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
• Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L).
• Prior treatment with at least one prior Novel Hormone Therapy (NHT), defined as second-generation anti-androgen therapies that include, but are not limited to, abiraterone acetate, enzalutamide, apalutamide, and darolutamide.
• Must be eligible for therapy with 177Lu-PSMA-617 and have ≥ 1 PSMA-positive lesion per treating investigator.
• Must have progressive mCRPC per the treating investigator.
• ECOG Performance Status ≤ 1.
• Adequate organ function as defined as:
‣ Hematologic:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support
∙ White blood cell count ≥ 3000/µL.
∙ Platelet count ≥ 100,000/µL
∙ Hemoglobin ≥ 9g/dL
∙ Serum albumin ≥ 2.5 g/dl
∙ PT/INR or partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN
⁃ Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
∙ For subjects with Gilbert's disease: ≤ 3x ULN
∙ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
⁃ Renal:
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
∙ Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula Males: ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72)
• Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment in accordance with section 5.4.2.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• Patients must have a life expectancy \>3 months.