Pasritamig: Teaching Your Own T Cells to Find Prostate Cancer
Study Details | NCT07225946 | A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer | ClinicalTrials.gov
Research Watch · Immunotherapy
A first-in-class bispecific antibody homes in on a prostate-specific "beacon" called KLK2 — and after skipping Phase 2, it is now in two Phase 3 trials.
BLUF — Bottom Line Up Front
Pasritamig (JNJ-78278343) is an experimental immunotherapy that grabs a T cell with one hand and a prostate-cancer cell with the other, forcing the immune system to attack. In its first human trial it was unusually gentle — cytokine release syndrome stayed mild and infrequent, no tocilizumab rescue was needed, and it can be given as an outpatient IV once every six weeks. About 42% of heavily pretreated men saw their PSA fall by half, with disease control lasting a median of roughly 8 months. New data in 2026 show it pairs safely with docetaxel chemotherapy, pushing PSA-50 responses to ~65%. It has FDA Fast Track status (and Breakthrough Therapy designation in China) and has advanced directly into two Phase 3 trials now enrolling. It is not yet approved, responses on scans remain modest, and long-term survival benefit is still unproven — but KLK2 has become one of the most promising new targets in prostate cancer.
For men whose prostate cancer has stopped responding to hormonal therapy and chemotherapy, the treatment shelf gets thin fast. A drug called pasritamig represents a genuinely different approach — not another hormone blocker or another cytotoxic poison, but a way of pointing the body's own immune system at the tumor with a precision that engineers can appreciate. As of mid-2026 it is one of the most closely watched agents in advanced prostate cancer, and the pace of its development has been striking.
What It Is, in Plain Terms
Pasritamig is a T-cell-redirecting bispecific antibody. Think of an ordinary antibody as a device with one connector. A bispecific antibody has two different connectors on the same molecule. One end latches onto CD3, a docking port found on every cytotoxic T cell — the immune system's assassins. The other end latches onto human kallikrein 2 (KLK2), a protein sitting on the surface of prostate cancer cells.
The elegance is in the target selection. KLK2 is a close cousin of PSA, and like PSA it is made almost exclusively by prostate tissue — there is very little of it anywhere else in the body. That specificity is the whole game in this class of drug: it lets you switch on a T-cell attack that lands on prostate cells and largely spares everything else. In systems terms, KLK2 is a clean signal with a low noise floor.
Mechanism — how the two-armed antibody works
The drug forms a physical bridge between immune cell and cancer cell. No genetic engineering of the patient's cells is required — this is an off-the-shelf antibody given by infusion, unlike CAR-T therapy.
The First-in-Human Results (Phase 1)
The foundational data come from a Phase 1 first-in-human study (NCT04898634), presented at the 2025 ASCO Annual Meeting by Dr. Capucine Baldini of Institut Gustave Roussy in France, and published the same day in the Journal of Clinical Oncology. This was a dose-finding study — its main job was to establish safety and a recommended dose, not to prove a survival benefit.
By the March 2025 data cut, 174 men had received at least one dose. These were not early-stage patients: the median age was 69, and they had already been through a median of four prior therapies (ranging up to thirteen), including hormonal agents, taxane chemotherapy, and in some cases Pluvicto-style PSMA radioligand therapy. This is roughly the same profile as many IPCSG members who have exhausted standard options.
Investigators settled on a recommended Phase 2 dose (RP2D) using a "step-up" schedule to ease the body in — a small 3.5 mg dose on Day 1, an 18 mg dose on Day 8, then a full 300 mg intravenous dose every six weeks. Notably, spacing the full dose out to once every six weeks appeared to keep the T cells from becoming "exhausted," which improved rather than diminished the effect — a counter-intuitive result worth flagging.
| Measure | Result | What it means |
|---|---|---|
| PSA dropped ≥50% (PSA-50) | 42.4% | 14 of 33 men at the recommended dose; ~36% had a confirmed, durable drop |
| Tumor shrinkage on scans (ORR) | 8.3% | Among 84 men with measurable disease — a modest figure, and an honest caveat |
| Duration of response | ~8.9 mo | How long responses lasted, on median |
| Radiographic progression-free survival | ~7.9 mo | Time before the cancer visibly advanced, on median |
The gap between the strong PSA responses and the modest scan-based response rate is real and worth understanding. PSA is an early, sensitive readout of biological activity; measurable tumor shrinkage on imaging is a higher bar, especially in prostate cancer, which often spreads to bone where "measurable" lesions are harder to score. The durability of disease control — not dramatic shrinkage — is where the encouragement lies in this dataset.
The Headline: An Immunotherapy That Behaves Itself
The most important finding may be on the safety side. T-cell engagers as a class are notorious for cytokine release syndrome (CRS) — an immune over-reaction that can cause fever, plummeting blood pressure, and, in severe cases, requires hospitalization and rescue drugs like tocilizumab. It is the main reason many of these drugs are confined to specialized centers.
Why clinicians took notice
At the recommended dose, CRS occurred in fewer than 10% of patients and was entirely Grade 1 (the mildest kind), with no tocilizumab required. There were no drug-related deaths, no neurological toxicity (ICANS), and only about 10% of patients across the whole study had a serious (Grade 3+) treatment-related side effect. The most common complaints were infusion reactions and fatigue.
That tolerability is what makes the every-six-weeks, outpatient schedule possible — and that, in turn, is what could let a T-cell engager be used in an ordinary community oncology office rather than only at a major academic center. For patients who do not live near a big cancer hospital, that logistical point is not a footnote; it is the difference between access and no access. Additional laboratory analyses presented at the ESMO 2025 congress in Berlin supported the biology behind the six-week schedule.
2026 Update: Adding Chemotherapy to the Mix
In February 2026, Johnson & Johnson reported early results from a Phase 1b study (NCT05818683) combining pasritamig with docetaxel, the standard chemotherapy for this disease, first presented at the 2026 ASCO Genitourinary Cancers Symposium. Among 51 men whose cancer had progressed after hormonal therapy (about 45% had already had a taxane):
- PSA fell by half or more in 64.7% of men overall — and in 75% of those who had never had a taxane before.
- 39% saw PSA drop by 90% or more — a deep response.
- The safety profile matched docetaxel given alone, with no new or unexpected signals from adding the antibody.
The engineering takeaway: adding pasritamig to chemotherapy appears to raise the response rate substantially without adding a meaningful new toxicity burden — the kind of clean additive result that justifies a larger, definitive trial.
Where It Stands: Two Phase 3 Trials, No Phase 2
On the strength of the Phase 1 data, pasritamig did something unusual — it skipped Phase 2 entirely and jumped to Phase 3, the large randomized studies that regulators need to see before approval. Two are now recruiting:
NCT07164443 · started Sep 2025
KLK2-comPAS
Pasritamig plus best supportive care versus placebo plus best supportive care, in late-line mCRPC after standard options are exhausted. Double-blind. The primary goal is overall survival — the gold-standard endpoint. Targeting roughly 663 participants.
NCT07225946 · verified Jun 2026
KLK2-PASenger
Pasritamig plus docetaxel versus docetaxel alone, in men who have progressed after a hormonal (ARPI) agent but have not yet had chemotherapy. Open-label. The primary goal is radiographic progression-free survival — beating docetaxel's historical ~8.5-month mark.
Between them, these two trials test the drug both by itself in end-stage disease and earlier, alongside chemotherapy. Members interested in participating can look up either trial by its NCT number on ClinicalTrials.gov, or ask their oncologist whether a site is enrolling near them.
The Bigger Picture — and the Competition
Pasritamig is the most advanced drug aimed at KLK2, but it is not alone. KLK2 is increasingly viewed as the next major prostate-cancer target after PSMA (the target of Pluvicto) and STEAP1. Other players are moving in — for example, a bispecific called EM1031 from China's Anmai Biotech was licensed to Juri Biosciences in a 2025 deal worth up to $210 million, and a separate Phase 3 program from BioNTech (BNT324) is testing a different agent against docetaxel. The competitive interest is itself a signal that serious money believes KLK2-directed immunotherapy will matter.
Honest caveats — read before you get your hopes too high
- Pasritamig is investigational and not FDA-approved. It is available only through clinical trials.
- The impressive numbers are from early, single-arm studies. Until the randomized Phase 3 trials read out, we cannot say it helps men live longer.
- Tumor-shrinkage rates on scans were modest (~8%); the story here is durable disease control and PSA response, not dramatic imaging responses.
- FDA Fast Track speeds up review; it is not an approval or an endorsement of effectiveness.
- We found no litigation, court filings, or regulatory disputes tied to the pasritamig program as of this writing — its path so far has been scientific and regulatory, not legal.
What This Means for IPCSG Members
Pasritamig is worth knowing about for three practical reasons. First, if you have run through hormonal therapy and chemotherapy, one of these two Phase 3 trials may be an option — the combination trial in particular is aimed at men who have not yet had chemo. Second, its gentle safety profile and every-six-weeks outpatient schedule are exactly the features that make a therapy livable, not just effective. Third, it is an early sign that the "immune redirection" strategy that has transformed some blood cancers is finally gaining traction in prostate cancer, where it has historically struggled.
As always, discuss any trial with your own oncologist, who can weigh your specific disease, prior treatments, and overall health. This article is educational and is not medical advice.
Verified Sources
- Baldini C, Vinceneux A, Robbrecht DGJ, et al. "Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC)." Journal of Clinical Oncology. 2025;43(16_suppl):5017. doi:10.1200/JCO.2025.43.16_suppl.5017. https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5017
- Klaassen Z. "ASCO 2025: Phase 1 Study Results of JNJ-78278343 (Pasritamig) in mCRPC." UroToday, June 2025. https://www.urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/160809-asco-2025-phase-1-study-results-of-jnj-78278343-pasritamig-in-mcrpc.html
- Johnson & Johnson. "Johnson & Johnson unveils first-in-human results for pasritamig, showing early anti-tumor activity in prostate cancer." Press release, June 1, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnson-unveils-first-in-human-results-for-pasritamig-showing-early-anti-tumor-activity-in-prostate-cancer
- OncLive. "Pasritamig Displays Safety, Durable Disease Control in Heavily Pretreated mCRPC." https://www.onclive.com/view/pasritamig-displays-safety-durable-disease-control-in-heavily-pretreated-mcrpc
- Johnson & Johnson. "Early study results from Johnson & Johnson show promising antitumor activity with combination of pasritamig and docetaxel in advanced prostate cancer." Press release, Feb 26, 2026. https://www.jnj.com/media-center/press-releases/early-study-results-from-johnson-johnson-show-promising-antitumor-activity-with-combination-of-pasritamig-and-docetaxel-in-advanced-prostate-cancer
- OncLive (Doherty K). "Pasritamig Plus Docetaxel Produces Strong Efficacy and Safety Data in mCRPC, Moves Into Phase 3 Study." June 2026 (features David R. Wise, MD, PhD). https://www.onclive.com/view/pasritamig-plus-docetaxel-produces-strong-efficacy-and-safety-data-in-mcrpc-moves-into-phase-3-study
- BioPharm International. "Pasritamig Demonstrates Positive Antitumor Activity in Combination with Docetaxel in Advanced Prostate Cancer." May 2026. https://www.biopharminternational.com/view/pasritamig-demonstrates-positive-antitumor-activity-combination-docetaxel-advanced-prostate-cancer
- Urology Times. "FDA grants fast track designation to pasritamig for mCRPC." May 2026. https://www.urologytimes.com/view/fda-grants-fast-track-designation-to-pasritamig-for-mcrpc
- ClinicalTrials.gov. "KLK2-PASenger: A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With mCRPC." NCT07225946. https://clinicaltrials.gov/study/NCT07225946
- ClinicalTrials.gov. "KLK2-comPAS: A Study of Pasritamig Versus Placebo in Late Line mCRPC." NCT07164443. https://clinicaltrials.gov/study/NCT07164443
- ClinicalTrials.gov. "A Study of Pasritamig (JNJ-78278343) in Combination With Other Agents for Metastatic Prostate Cancer" (Phase 1b). NCT05818683. https://clinicaltrials.gov/study/NCT05818683
- ClinicalTrials.gov. Phase 1 first-in-human study of JNJ-78278343. NCT04898634. https://clinicaltrials.gov/study/NCT04898634
- Kactus Biosystems. "KLK2: The New Promising Target for Prostate Cancer" (background on KLK2 target and competitive landscape, incl. EM1031). https://kactusbio.com/blogs/recombinant-proteins/klk2-promising-target-for-prostate-cancer
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