The novel KLK2 T-cell engager pasritamig in combination with docetaxel displayed promising clinical activity and was well tolerated in patients with metastatic castration-resistant prostate cancer (mCRPC), warranting further study in this patient population, according to David R. Wise, MD, PhD.1
Findings from a phase 1b study (NCT05818683) presented in a poster during the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) demonstrated that 64.7% of patients who received the combination (n = 51) achieved a minimum 50% reduction of prostate-specific antigen levels (PSA50), and 39.2% of patients experienced a 90% or more reduction in PSA levels (PSA90). The PSA50 rate in patients with bone-only metastases (n = 17) was 88.2%, and the PSA90 rate was 76.5%.
“We know docetaxel has [an approximately] 45% PSA50 [response] rate, so [an 88.2% PSA50 response rate with the combination for patients with bone-only metastases] is substantially better,” Wise explained in an interview with OncLive®. “The pasritamig [monotherapy] PSA50 rate is approximately 35% to 37%, so we’re seeing a clear additive effect and potentially even some synergy [by adding docetaxel].”
Wise is the service chief of the Genitourinary Medical Oncology Program and the codirector of the Department of Medicine Clinical Investigator Track at NYU Langone Health, as well as an associate professor in the Department of Medicine and the Department of Urology at NYU Grossman School of Medicine, in New York, New York.
In the interview, Wise discussed the background and design of the phase 1b trial, the notable data from this study presented at ASCO GU, and the potential future role of pasritamig in the mCRPC treatment landscape.
Phase 1b Trial of Pasritamig Plus Docetaxel in mCRPC: Key Takeaways • Pasritamig is a novel KLK2 T-cell engager that has displayed activity and tolerability as monotherapy in mCRPC. • Data from a phase 1b study showed that pasritamig plus docetaxel produced PSA50 and PSA 90 rates of 64.7% and 39.2%, respectively. • The combination is now being examined in the phase 3 KLK2-PASenger trial, which is actively enrolling patients.
- Pasritamig is a novel KLK2 T-cell engager that has displayed activity and tolerability as monotherapy in mCRPC.
- Data from a phase 1b study showed that pasritamig plus docetaxel produced PSA50 and PSA 90 rates of 64.7% and 39.2%, respectively.
- The combination is now being examined in the phase 3 KLK2-PASenger trial, which is actively enrolling patients.
OncLive: What was the clinical rationale for examining pasritamig plus docetaxel in mCRPC?
Wise: In the phase 1 trial testing pasritamig, we found some really remarkable evidence of activity, along with good tolerability. What’s unique about this molecule is that it has not been associated with high-grade cytokine release syndrome [CRS] in the patients studied, and CRS has been one of the major barriers for bispecifics.
This was a molecule we wanted to bring into the broader mCRPC landscape and assess in combination with existing active agents. In this study, we combined it with docetaxel. Notably, many newer agents are difficult to combine with docetaxel because they are associated with high rates of CRS or bone marrow toxicity, which is not an ideal profile for combination. This agent does not have either of those issues, which formed the basis for this approach.
What were the key design characteristics of the phase 1b trial?
This was a single-arm study in which we treated patients with mCRPC who had received at least 1 androgen receptor pathway inhibitor [ARPI]. Patients may or may not have received lutetium Lu 177 vipivotide tetraxetan [Pluvicto] and may or may not have had prior docetaxel. The analysis was stratified based on whether patients were taxane-naive or taxane-resistant.
Patients were treated with both agents, beginning with step-up dosing of the bispecific prior to initiation of docetaxel. The full dose was then given concurrently, starting on cycle 1, day 1, alongside docetaxel. Pasritamig was administered every 6 weeks and docetaxel every 3 weeks, aligning the treatment schedule.
What safety data were reported from this study during ASCO GU?
The adverse effect profile [for pasritamig plus docetaxel] largely mirrored what you would expect from docetaxel monotherapy and prior experience with pasritamig, making this a well-tolerated combination. We did not observe high-grade CRS, consistent with the phase 1 experience, and the toxicity profile of docetaxel was as expected. There were no new synergistic or concerning safety signals, which was reassuring.
What are the next steps for evaluating pasritamig in mCRPC?
[Based on] the clean safety profile and promising efficacy signals [seen with this pasritamig regimen], the program has moved directly into the phase 3 KLK2-PASenger trial [NCT07225946]. [This is] a randomized, open-label trial comparing docetaxel plus pasritamig vs docetaxel alone in the post–ARPI [androgen receptor pathway inhibitor] mCRPC setting.2
This study is actively enrolling, and we are hopeful it will demonstrate an improvement in the durability of response for our patients.
How could pasritamig alter the clinical landscape of mCRPC if the phase 3 trial is successful?
Patients with mCRPC have many treatment options, but selecting the optimal therapy remains a major unmet need. One key question in the field is choosing between docetaxel and radioligand therapy, such as [lutetium Lu 177 vipivotide tetraxetan]. Recent randomized data suggest a benefit to starting with docetaxel in appropriate patients, reinforcing its role as a core component of treatment.
The challenge is that the duration of response with docetaxel is limited, with a [median\progression-free survival of [approximately] 8.5 months. We need strategies to extend that benefit. This is where pasritamig may fit in, as a drug that can be safely combined with docetaxel without overlapping toxicities.
If the phase 3 trial [data are] positive, this combination could offer a straightforward strategy of using 2 active agents together to improve outcomes. Beyond that, we are also hoping to see true synergy. There is evidence that docetaxel may modulate the tumor microenvironment to enhance T-cell activity, potentially improving the efficacy of bispecifics.
Ultimately, we hope this approach will not only be safe but also significantly improve the durability of response compared with either agent alone.
Disclosures: Wise reported holding stock and other ownership interests with Doximity; receiving honoraria from OncLive and ScientiaCME; holding consulting or advisory roles with Bayer, Janssen, K36, OncoC4, and Pfizer; and receiving travel, accommodations, and expenses from Bayer and Pfizer.
References
- Patel MR, Pachynski RK, Sandhu S, et al. Safety and efficacy of pasritamig (PAS) + docetaxel (DOCE) in participants with metastatic castration-resistant prostate cancer (mcrPc): initial results of a phase 1b study. J Clin Oncol. 2026;44(suppl 7):171. doi:10.1200/JCO.2026.44.7_suppl.171
- A study of pasritamig with docetaxel versus docetaxel in participants with metastatic castration-resistant prostate cancer (KLK2-PASenger). ClinicalTrials.gov. Updated March 13, 2026. Accessed April 6, 2026. https://clinicaltrials.gov/study/NCT07225946
