JANX007 Shows Promising Efficacy, Safety in Phase 1 Trial Update

An update of the phase 1 ENGAGER-PSMA-01 trial (NCT05519449) shows that JANX007, a first-in-class, tumor-activated T-cell engager (TCE) targeting prostate-specific membrane antigen (PSMA) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) yields durable responses with a manageable safety profile.^1,2 

JANX007 treatment resulted in deep and durable prostate-specific antigen (PSA) reductions. For the 85 evaluable patients treated with a target dose of 2 mg or higher, the results were as follows:

• PSA50 (≥ 50% reduction): 73%
• PSA90 (≥ 90% reduction): 26%

Among 27 patients with measurable disease at baseline treated with 2 mg or higher, the objective response rate was 30%. Durable responses were observed in patients with both bone-only disease and those with soft tissue metastases. 

The radiographic progression-free survival (rPFS) profile for JANX007 compares favorably with competitor data for both commercial and investigational therapies. As of October 15, 2025, the median rPFS has been maintained as the patient set has expanded. The median rPFS for all patients treated with 2 mg or higher (n = 108) was 7.3 months. In the May 2025 cohort (n = 9), the rPFS was 7.9 months. Patients treated every week (n = 29) had a rPFS of 7.9 months, and patients treated every 2 weeks (n = 19) had a median rPFS of 8.9 months. The 6-month PFS per these 4 patient groups was 51%, 78%, 76%, and 54%, respectively. 

An analysis of radioligand therapy-naive patients suggests that disease burden inversely correlates with rPFS durability. Patients with a low disease burden (n = 24) had a median rPFS of 10.5 months; patients with a high disease burden (n = 39) had a median rPFS of 7.3 months. 

Safety Profile of JANX007

Although cytokine release syndrome (CRS) was the most common treatment-related adverse event (TRAE), it was predominantly low-grade and manageable. Of the total patients, 96% experienced CRS (n = 105/109). Of the patients who experienced CRS, 33% had grade 1 CRS, 55% had grade 2 CRS, and 8% had grade 3 or higher CRS. The onset and duration of CRS were predictable, with resolution typically occurring within 1 day.¹

Other TRAEs included diarrhea (all grades, 61%), nausea (all grades, 55%), and vomiting (all grades, 53%). 

Based on safety evaluations in later treatment cycles (cycle 3+), the 12-mg target dose was deprioritized due to higher rates of grade 3 or higher TRAEs.

Study Design

The ongoing phase 1a/1b clinical trials for JANX007 were designed to establish a safe and effective dose and regimen for pivotal studies.

JANX007 is a first-in-human, tumor-activated TCE designed to treat prostate cancer by targeting PSMA, a clinically validated cell surface antigen highly expressed in prostate cancer metastases. Although other PSMA-targeting TCEs have shown antitumor activity, their development has often been limited by significant AEs, particularly CRS.¹

The core objectives of phase 1 included dose escalation and expansion in patients with mCRPC, evaluating the timing and dose of dexamethasone and/or tocilizumab to maintain a grade 1/2 CRS profile, determining the target dose and dose interval, and evaluating the efficacy and safety for taxane-naive patients. 

The target doses were determined to be 6 mg and 9 mg. These regimens showed the best balance of safety and efficacy. 

The median age of patients was 68 years (range, 46-86). Patients had an ECOG performance status of 0 (n = 52) or 1 (n = 56). All of the patients (100%) were PSMA-positive at baseline. Patients had a median of 4 prior lines of therapy (range, 1-9). The majority of patients had bone metastases (89%).

Early data from the phase 1b expansion study in taxane-naive patients is highly encouraging. Patients receiving the 6-mg weekly regimen demonstrated early and deep PSA reductions. Among the first evaluable patients, 100% achieved PSA50 and 63% achieved PSA90.²

Next Steps in Research

JANX007 will be evaluated as a monotherapy and in combination with darolutamide (Nubeqa) for taxane-naive, pre-Lu 177 vipivotide tetraxetan (177Lu-PSMA-617; Pluvicto) patients with mCRPC. Janux Therapeutics, developer of the agent, will also evaluate JANX007 in PARP inhibitor–refractory patients as a potential route to an expedited approval.³

“The early data with JANX007 are highly encouraging,” said Eleni Efstathiou, MD, section chief, genitourinary medical oncology, at Houston Methodist Cancer Center in Texas and investigator on the trial, in a news release.³ “I am deeply committed to this program and inspired by its potential to transform care for [patients with mCRPC], especially as its potential in earlier-line mCRPC treatment is explored.”

REFERENCES

1. Creating transformative medicines to improve patients’ lives. JANX007 phase 1 clinical update. Janux Therapeutics. December 1, 2025. Accessed December 3, 2025. https://tinyurl.com/y4fzccer 

2. Study of JANX007 in subjects with metastatic castration-resistant prostate cancer (ENGAGER-PSMA-01). ClinicalTrials.gov. Updated November 14, 2025. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT05519449 

3. 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 3, 2025. https://tinyurl.com/25crahdp