LORIKEET: A phase 2, randomized, open-label study of lorigerlimab plus docetaxel versus docetaxel alone in patients with metastatic castration-resistant prostate cancer (mCRPC).

TPS242 Background: Lorigerlimab is an investigational bispecific, Fc-bearing (IgG4) DART molecule that binds PD-1 and CTLA-4. Lorigerlimab is engineered to enhance CTLA-4 binding in the tumor microenvironment (TME) while minimizing off-tumor CTLA-4 binding in normal tissue. 2 A phase 1 study of lorigerlimab monotherapy in 162 patients with advanced solid tumors (NCT03761017) demonstrated a manageable safety profile. The objective response rate (ORR) among 35 patients with heavily pretreated mCRPC and measurable disease was 25.7%. 1 Chemoimmunotherapy combination regimens have demonstrated improved outcomes over chemotherapy or immune checkpoint inhibitors given alone in multiple cancers. Although recent data showed lack of survival improvement when anti-PD-1 antibody was combined with docetaxel in mCRPC, 3 dual blockade of PD-1 and CTLA-4 with lorigerlimab may be an effective strategy to potentiate host immune responses in the TME with limited CTLA-4-associated toxicities. In addition to direct antitumor activity, docetaxel may stimulate antitumor immunity and enhance the immunomodulating effects of lorigerlimab. The phase 2 LORIKEET study will compare the combination of lorigerlimab plus docetaxel versus docetaxel alone in patients with mCRPC. Methods: Approximately 150 patients will be randomized 2:1 to lorigerlimab (6mg/kg Q3W) combined with docetaxel (75 mg/m2 Q3W) and prednisone (5mg BID) versus docetaxel and prednisone alone. Patients are stratified by the presence of visceral disease (yes vs no) and geographic region (North America vs other). Key eligibility criteria include age ³ 18; ECOG performance status 0 or 1; disease progression by PCWG3 criteria following prior androgen receptor axis-targeted therapy (e.g., abiraterone, enzalutamide, apalutamide); no prior taxane chemotherapy for mCRPC;immune checkpoint inhibitors. The primary endpoint is radiographic progression free survival (rPFS) per PCWG3 criteria. Secondary endpoints include ORR, duration of response, PSA response, safety, overall survival, and HRQOL measures including change in pain severity and time to first symptomatic skeletal events. Eligible patients randomized to receive docetaxel and prednisone alone who experience radiographic progression may remain on study and receive lorigerlimab monotherapy. Enrollment is ongoing. 1. Luke, ASCO-GU 2023, Abstract 155. 2. Berezhnoy, PMID 33377134. 3. Petrylak, ASCO-GU 2023, Abstract 19. Clinical trial information: NCT05848011 .