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Pasritamig Displays Safety, Durable Disease Control in Heavily Pretreated mCRPC

Pasritamig was safe and produced durable responses in heavily pretreated metastatic castration-resistant prostate cancer.

Prostate cancer | Image Credit: Sebastian Kaulitzki © stock.adobe.com

Prostate cancer | Image Credit: Sebastian Kaulitzki © stock.adobe.com

Treatment with the KLK2 x CD3 bispecific T-cell engager pasritamig (JNJ-78278343) generated durable disease control and displayed a tolerable safety profile in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), according to data from a phase 1 trial (NCT04898634) presented at the 2025 ASCO Annual Meeting.

Findings demonstrated that among patients in the recommended phase 2 dose (RP2D) efficacy population (n = 33), a 50% reduction in prostate-specific antigen (PSA) levels (PSA50) was observed in 42.4% of patients at any point. The confirmed PSA50 rate was 36.4%. PSA decreases in this population occurred as early as initial step-up dosing.

Among patients in the trial’s all-treated population who had measurable disease at baseline (n = 84), the overall response rate was 8.3%, and the median duration of response was 8.9 months (95% CI, 3.6-not evaluable [NE]). One patient without measurable disease experienced a complete response.

Regarding safety in the all-treated population (n = 174), any-grade treatment-related adverse effects (TRAEs) occurred in 82.8% of patients, serious TRAEs were reported in 6.9% of patients, and grade 3 or higher TRAEs were observed in 9.8% of patients. TRAEs led to treatment discontinuation in 1 patient (0.6%). In patients treated at the RP2D (n = 45), the rates of any-grade TRAEs, serious TRAEs, and grade 3 or higher TRAEs were 60.0%, 4.4%, and 4.4%, respectively. No patients treated at the RP2D discontinued treatment due to TRAEs.

“Currently, multiple pivotal studies using [pasritamig] are being developed,” lead study author Capucine Baldini, MD, of the Drug Development Department at Institut Gustave Roussy in Villejuif, France, said in a presentation of the data.

Pasritamig Background and Study Design

The first-in-class bispecific T-cell engager targets KLK2, which is a novel target expressed by prostate cancer cells and has limited expression on normal tissue. By binding to KLK2 on prostate cancer cells and CD3 on T cells, the agent activates T cells and drive cancer cell lysis.

The first-in-human, dose-escalation and -expansion study is enrolling patients with mCRPC who received prior treatment with an androgen receptor pathway inhibitor (ARPI) and/or chemotherapy. Prior treatment with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is permitted. In dose expansion specifically, patients need to have a PSA level of more than 2 ng/mL and no visceral disease. An ECOG performance status of 0 or 1 is necessary for all patients.

During dose escalation, 7 different total doses and step-up dosing regimens were evaluated. Step-up dosing was utilized to mitigate cytokine release syndrome (CRS), and treatment also shifted to intravenous (IV) dosing vs subcutaneous injections to allow for higher doses with fewer injections. The RP2D is administered via outpatient IV administration, with pasritamig given at 3.5 mg as the first step-up dose on day 1 of cycle 1; 18 mg on day 8 of cycle 1 as the second step-up dose; and at 300 mg on day 15 and then once every 6 weeks.

In the all-treated population, the median age was 69.0 years (range, 36-89). Patients had an ECOG performance status of 0 (50.6%) or 1 (49.4%); and a baseline PSA level of 74.8 ng/mL (range, 0.0-2612.0). Disease locations included bone (88.4%) and lymph node (46.8%); 24.3% of patients had visceral metastases, including 10.4% with liver metastases.

Patients received a median of 4.0 prior lines of therapy (range, 1.0-13.0), and prior treatments comprised an ARPI (99.4%), taxane-based chemotherapy (78.2%), and Lu 177 prostate-specific membrane antigen radioligand therapy (17.8%). Notably, 26.4% of patients received 1 taxane-based chemotherapy regimen, and 51.7% received more than 1.

Additional RP2D Efficacy and Safety Data

Findings also showed that in the RP2D efficacy population, patients experienced a median radiographic progression-free survival (rPFS) of 7.85 months (95% CI, 2.89-NE). At data cutoff, 21.2% of patients in this population remained on treatment. PSA50 responses and disease control were observed irrespective of prior treatments.

In the safety-evaluable population for the RP2D, CRS occurred in 8.9% of patients, with all instances being grade 1. No tocilizumab (Actemra) prophylaxis was required. Infusion-related reactions were reported in 24.4% of patients, and these adverse effects were managed with antipyretics; no steroids or epinephrine were required.

No dose-limiting toxicities were reported with the RP2D, and along with no treatment discontinuation, TRAEs did not lead to any instances of dose reduction, death, or immune effector cell–associated neurotoxicity syndrome. The only grade 3 TRAEs were transient elevated alanine and aspartate aminotransferases levels, and neutropenia.

Disclosures: Baldini has consulting or advisory roles with Bicycle Therapeutics, Janssen Oncology, and Rising Tide Foundation. She has also received research funding from Foundation BMS and has provided expert testimony for AbbVie, AstraZeneca, Bristol-Myers Squibb, and MSD Oncology. She has received travel, accommodations, and expenses from Amgen, Janssen Oncology, MSD Oncology, and Roche/Genentech.

Reference

Baldini C, Vinceneux A, Robbrecht D, et al. Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2025;43(suppl 16):5017. doi:10.1200/JCO.2025.43.16_suppl.5017


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