Phase I/II Study of CDK4/6 Inhibition With Abemaciclib to Upregulate PSMA Expression Prior to 177Lu-PSMA-617 Treatment in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Previously Treated With Novel Hormonal Agents and Chemotherapy
Vadim S Koshkin
Summary
This phase I/II trial tests the safety, side effects, and best dose of abemaciclib and whether it works before 177Lu-PSMA-617 in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Abemaciclib is in a class of medications called kinase inhibitors. It is highly selective inhibitors of cyclin-dependent kinase 4 and 6, which are proteins involved in cell differentiation and growth. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. Radioligand therapy uses a small molecule (in this case 177Lu-PSMA-617), which carries a radioactive component to destroys tumor cells. When 177Lu-PSMA-617 is injected into the body, it attaches to the prostate-specific membrane antigen (PSMA) receptor found on tumor cells. After 177Lu-PSMA-617 attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving abemaciclib before 177Lu-PSMA-617 may help 177Lu-PSMA-617 kill more tumor cells.
Description
PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RP2D) for abemaciclib given as lead-in treatment prior to lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) for each treatment cycle, as well as dose limiting toxicities (DLTs) of this combination regimen. (Part A) II. To determine the change in prostate-specific membrane antigen (PSMA) uptake on gallium Ga 68 gozetotide (68Ga-PSMA-11) positron emission tomography (PET) scan following fourteen days of priming with abemaciclib treatment, relative to the pre-treatment baseline scan. (Part B (Expanded Cohort)). SECONDARY O…