JANX007 Displays Encouraging Safety/Efficacy in Metastatic CRPC

Patients treated in the trial experienced durable responses, with those treated on a displaying a median radiographic progression-free survival (rPFS) ranging from 7.9 to 8.9 months.

JANX007, a prostate-specific membrane antigen (PSMA)–directed tumor activated T-cell engager (TRACTr), exhibited encouraging safety and preliminary efficacy among patients with taxane-naive metastatic castration-resistant prostate cancer (CRPC) in the phase 1b ENGAGER-PSMA-01 trial (NCT05519449), according to a news release from the developer, Janux Therapeutics.1

Data from the trial revealed that, as of the data cutoff date of October 15, 2025, 109 patients were treated with the investigational agent across the phase 1a and 1b dose-escalation and dose-expansion trials, the former of which included previously treated patients with at least 4 lines of prior therapy and the latter of which did not include those who received prior taxane-based therapy for their CRPC. Furthermore, patients across both trials exhibited high prostate-specific antigen (PSA) response rates, and confirmed or unconfirmed partial responses were observed in 8 of 27 (30%) of patients who were evaluable per RECIST v1.1 criteria.

Moreover, patients treated in the trial experienced durable responses, with those treated on a weekly or biweekly schedule displaying a median radiographic progression-free survival (rPFS) ranging from 7.9 to 8.9 months; rPFS outcomes favored the biweekly group. Among patients not previously treated with taxanes, rapid and deep PSA reductions were observed, and incidences of cytokine release syndrome (CRS) were primarily grades 1 or 2 and seen in cycle 1 of treatment. Furthermore, the potential for improved rPFS was observed in a tumor burden analysis among patients treated in earlier lines of therapy.

“We are pleased JANX007 achieved durable responses with a manageable safety profile that compares favorably to both approved and investigational therapies in [metastatic] CRPC. Additionally, we found that the ability to transition patients to [biweekly] dosing may provide meaningful convenience advantages,” David Campbell, PhD, president and chief executive officer at Janux Therapeutics, said in the news release on the phase 1 JANX007 findings.1 “We look forward to evaluating the potential for JANX007 in earlier-line [metastatic] CRPC, where improved tolerability and durability could have an even greater impact.”

Patients in the phase 1a portion of the trial received escalating doses of JANX007 intravenously in 21- or 28-day cycles until the maximum tolerated dose was determined.2 A backfill expansion arm treated patients at doses previously deemed tolerable. Four monotherapy expansion parts, A through D, were initiated, with patients dosed at the preliminary recommended phase 2 dose, as well as a combination expansion arm in which patients were treated with darolutamide (Nubeqa) in addition to JANX007.

The primary end points of the phase 1 study were dose-limiting toxicities and adverse effects. Secondary end points included pharmacokinetics, pharmacodynamics, duration of response, PSA response, radiographic PFS, overall response rate, and overall survival.

Patients 18 years and older with histologically or cytologically confirmed adenocarcinoma of the prostate and adequate organ function were eligible for enrollment on the trial. For the dose-escalation and backfill portion of the study, patients must have had disease that progressed following at least 1 novel anti-androgen therapy and 1 taxane-containing regimen; however, those who have actively refused or were medically unsuitable to receive taxane were eligible for trial enrollment.

Those deemed ineligible for enrollment included those who received a prior solid organ transplant, prior PSMA-targeted CAR T-cell therapy, or PSMA/CD3 T-cell engaging bispecific antibodies or radioligands, and those with clinically significant cardiovascular disease. Additionally, those with an active clinically significant infection, medical condition, or clinically laboratory abnormality with the potential to interfere with safety or efficacy assessments of the study agents were excluded from trial enrollment.

References

1. Janux announces encouraging efficacy and safety profile from ongoing phase 1 clinical trial for JANX007 in mCRPC. News release. Janux Therapeutics. December 1, 2025. Accessed December 2, 2025. https://tinyurl.com/4ndb78je
2. Study of JANX007 in subjects with metastatic castration-resistant prostate cancer (ENGAGER-PSMA-01). ClinicalTrials.gov. Updated November 14, 2025. Accessed December 2, 2025. https://tinyurl.com/4cvwcdeu