A phase 3 randomized, open-label study of pasritamig (JNJ-78278343), a T-cell engager targeting human kallikrein-2, with docetaxel versus docetaxel for metastatic castration-resistant prostate cancer.

TPS5139 Background: Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease with high morbidity and a median overall survival of approximately two years. Human kallikrein 2 (KLK2) is highly and specifically expressed in normal and malignant prostate tissue, including late stage mCRPC. Pasritamig (PAS) is a first-in-class bispecific T-cell-engager that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. In the Phase 1b study (NCT05818683), pasritamig was combined with docetaxel (DOCE) to treat patients with mCRPC. The safety profile of PAS+DOCE was shown to be consistent with previous studies of DOCE and no cytokine release syndrome of any grade was reported (0 of 51 patients). Promising anti-tumor activity was observed in both taxane-naïve and heavily pretreated patients. Methods: This global, randomized, open-label, phase 3 study (NCT07225946) evaluates the efficacy and safety of PAS in combination with DOCE versus DOCE alone in adult participants (≥18 years) with mCRPC. Approximately 800 participants will be randomized 1:1. Stratification factors include sites of metastases (on conventional imaging), lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, and prior poly(ADP-ribose) polymerase (PARP) inhibitor use. Key inclusion criteria are histologically or cytologically confirmed adenocarcinoma of the prostate, evidence of metastatic disease, and PSA or radiographic disease progression on 1-2 novel ARPI for any stage of prostate cancer. Key exclusion criteria include prior treatment with T-cell redirecting therapies, chemotherapy, or radiopharmaceutical therapy, uncontrolled central nervous system metastases, or significant comorbidities that could interfere with study participation. PAS is administered in the outpatient setting at a target dose of 300 mg IV Q6W with two step-up doses of 3.5 mg IV on day 1 and 18 mg IV on day 8. Participants in the DOCE alone arm will also receive continuous prednisone per label. The primary endpoint is radiographic progression-free survival assessed by blinded independent central review per Prostate Cancer Working Group 3 and RECIST v1.1 criteria. Key secondary endpoints include overall survival, time to symptomatic progression, time to subsequent therapy, and time to skeletal-related event. Safety, pharmacokinetics, biomarkers, and quality of life assessments will also be evaluated. The study is currently enrolling patients in the North and Latin Americas, European Union and Asia Pacific regions. Clinical trial information: 78278343PCR3003 .