(UroToday.com) The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting was host to a prostate, testicular, and penile cancers poster session. Dr. Rana McKay presented LK2-PASenger, an ongoing, randomized phase III study evaluating pasritamig versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after treatment with a novel hormonal agent (NHA).
Despite significant advances in the treatment of advanced prostate cancer, outcomes remain poor for patients with mCRPC following progression on androgen receptor pathway inhibitors. Delta-like ligand 3 (DLL3) has emerged as a promising therapeutic target in prostate cancer. DLL3 expression is highly restricted in normal tissues but is enriched in aggressive prostate cancer phenotypes, including treatment-emergent neuroendocrine prostate cancer and subsets of mCRPC. DLL3 expression has also been associated with resistance to androgen receptor-directed therapies, making it an attractive target for novel immunotherapeutic approaches.
Pasritamig is a DLL3-targeted bispecific T-cell engager designed to redirect cytotoxic T cells toward DLL3-expressing tumor cells. Early clinical studies have demonstrated encouraging antitumor activity with manageable safety, supporting further evaluation in larger randomized studies. The poster highlights that DLL3 expression has been identified across a spectrum of advanced prostate cancer subtypes and that responses to DLL3-directed therapy have been observed in heavily pretreated patients.
LK2-PASenger is a global, randomized, open-label phase III study enrolling approximately 800 patients with mCRPC who have progressed after treatment with an NHA and are considered candidates for chemotherapy. Patients are randomized in a 1:1 ratio to receive:
- Pasritamig
- Docetaxel
Randomization is stratified according to:
- Prior taxane exposure in the hormone-sensitive setting
- Presence of visceral metastases
- Geographic region
Eligible patients must have:
- Histologically confirmed adenocarcinoma of the prostate
- Evidence of metastatic disease
- Progressive mCRPC
- Ongoing androgen deprivation therapy
- ECOG performance status 0–1
- Adequate organ function
Key exclusion criteria include:
- Prior treatment with a DLL3-directed therapy
- Active or untreated central nervous system metastases
- Significant cardiovascular disease
- Active autoimmune disease requiring systemic therapy
- Other medical conditions that could interfere with study participation
The dual primary endpoints are:
- Overall survival (OS)
- Radiographic progression-free survival (rPFS) by blinded independent central review
Key secondary endpoints include:
- Objective response rate (ORR)
- Duration of response (DOR)
- Time to symptomatic progression
- Time to subsequent anticancer therapy
- Safety and tolerability
- Patient-reported outcomes
An important translational component of the study is the evaluation of DLL3 as a predictive biomarker. Tumor tissue and blood-based analyses will be performed to better characterize DLL3 expression patterns and identify patient populations most likely to derive benefit from treatment.
The poster highlights prior clinical experience supporting DLL3-directed therapies in prostate cancer. DLL3 expression has been observed in a meaningful proportion of advanced prostate cancers, particularly among tumors demonstrating neuroendocrine differentiation and treatment resistance. These observations provide strong biologic rationale for evaluating DLL3-targeted immunotherapy in earlier lines of mCRPC treatment.
Pasritamig is administered using a step-up dosing strategy designed to mitigate cytokine release syndrome and improve tolerability. Patients randomized to the experimental arm receive outpatient administration following the step-up phase. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or study discontinuation.
At the time of presentation, LK2-PASenger was actively recruiting globally, with participating sites across North America, South America, Europe, Asia, and Australia.
The investigators concluded that LK2-PASenger will determine whether DLL3-targeted immunotherapy can improve outcomes compared with standard docetaxel chemotherapy in patients with mCRPC progressing after NHA therapy. Given the continued need for novel treatment strategies beyond androgen receptor-directed approaches and the biologic relevance of DLL3 in advanced prostate cancer, this study represents an important effort to establish a new biomarker-driven therapeutic option in the post-NHA mCRPC setting.
Presented by: Rana R. McKay, MD, Professor of Medicine, Department of Medicine, University of California, San Diego Moores Cancer Center, La Jolla, CA, USA
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center, Tucson, AZ – @rksayyid on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026