KLK2-comPAS trial explores dual T-cell engagement in mCRPC

In this video, Kim Chi, MD, FRCP, discusses the rationale and design of the phase 3 KLK2-comPAS trial (NCT07164443) evaluating pasritamig, alone and in combination with JNJ-9401, in patients with metastatic castration-resistant prostate cancer (mCRPC) who have exhausted available life-prolonging treatment options.

The design of the study was presented at the 2026 European Society for Medical Oncology Annual Congress in Madrid, Spain as a trials in progress poster. Chi is a medical oncologist at BC Cancer in Vancouver, Canada, and a professor of medicine at the University of British Columbia.

According to Chi, the KLK2-comPAS trial builds on the potential of kallikrein-related peptidase 2 (KLK2) as a therapeutic target because of its expression in normal and malignant prostate tissue. Pasritamig is a bispecific antibody that engages CD3 on T cells and KLK2 on prostate cancer cells to stimulate a targeted immune response. Earlier-phase findings in heavily pretreated patients demonstrated encouraging antitumor activity and a favorable safety profile.² Notably, high-grade cytokine release syndrome (CRS) was not observed.

“One of the concerns around T cell engagers is that [they] can cause significant CRS, often sending patients even into intensive care units, for example, because of severe CRS,” Chi noted. “However, with pasritamig, we did not see that severe CRS associated with other T cell engagers. So it's very well-tolerated.”

The KLK2-comPAS study also incorporates JNJ-9401 (also referred to as JNJ-87189401), a T-cell engager targeting CD28 and prostate-specific membrane antigen (PSMA), with the goal of enhancing T-cell activation. Chi noted that preclinical findings suggest synergistic activity with the combination.

KLK2-comPAS is a global, randomized phase 3 study enrolling patients with mCRPC who have received available and appropriate life-prolonging therapies, including androgen receptor pathway inhibitors, taxane chemotherapy, radioligand therapy, and PARP inhibitors when indicated for patients with BRCA mutations. The initial study design compares pasritamig plus best supportive care with placebo plus best supportive care. An expanded second part will evaluate pasritamig alone, pasritamig plus JNJ-9401, and placebo, each alongside best supportive care.

The primary end point is overall survival, with secondary end points including radiographic progression-free survival, progression-free survival, time to symptomatic progression, and time to skeletal-related events.

_______

REFERENCES

1. Chi KN, Gedye C, Belkoff LH, et al. KLK2-comPAS: A phase 3, randomized, double-blind, placebo-controlled study of pasritamig plus best supportive care in mCRPC. Presented at: 2026 European Society for Medical Oncology Congress. October 23-27, 2026. Madrid, Spain. Poster 2388eTiP

2. Patel M. Safety and efficacy of pasritamig (PAS) + docetaxel (DOCE) in participants with metastatic castration-resistant prostate cancer (mcrPc): Initial results of a phase 1b study. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract 171. https://www.asco.org/abstracts-presentations/256425