JANX007 Demonstrates Promising Efficacy and Manageable Safety Profile in Phase 1 Metastatic Prostate Cancer Trial
核心洞察
JANX007, a first-in-class tumor-activated T-cell engager targeting PSMA (搜索), achieved a 73% PSA50 response rate and 30% objective response rate in 109 patients with metastatic castration-resistant prostate cancer (搜索).
The investigational therapy demonstrated durable responses with median radiographic progression-free survival ranging from 7.9 to 8.9 months, with biweekly dosing showing favorable outcomes.
Cytokine release syndrome (搜索) occurred in 96% of patients but was predominantly low-grade and manageable, with 88% experiencing grade 1-2 events that typically resolved within one day.
JANX007, a prostate-specific membrane antigen (搜索) (PSMA (搜索))-directed tumor activated T-cell engager (TRACTr), has demonstrated encouraging safety and preliminary efficacy in patients with metastatic castration-resistant prostate cancer (搜索) (mCRPC) in the ongoing phase 1b ENGAGER-PSMA-01 trial. The investigational therapy, developed by Janux Therapeutics, represents a first-in-class approach to treating advanced prostate cancer through tumor-activated T-cell engagement.
Strong Response Rates Across Patient Population
As of the October 15, 2025 data cutoff, 109 patients had been treated with JANX007 across the phase 1a and 1b dose-escalation and dose-expansion trials. Among 85 evaluable patients treated with a target dose of ≥2 mg, the therapy achieved a PSA50 response rate (≥50% reduction in prostate-specific antigen) of 73% and a PSA90 response rate (≥90% reduction) of 26%.
The objective response rate reached 30% among 27 patients with measurable disease at baseline who received ≥2 mg doses, with confirmed or unconfirmed partial responses observed per RECIST v1.1 criteria. Notably, durable responses were seen in patients with both bone-only disease and those with soft tissue metastases.
Favorable Progression-Free Survival Outcomes
The radiographic progression-free survival (rPFS) profile for JANX007 compares favorably with competitor data for both commercial and investigational therapies. The median rPFS for all patients treated with ≥2 mg (n = 108) was 7.3 months. Patients treated on weekly schedules achieved a median rPFS of 7.9 months, while those on biweekly dosing demonstrated a median rPFS of 8.9 months, with rPFS outcomes favoring the biweekly group.
A disease burden analysis revealed that patients with low disease burden (n = 24) achieved a median rPFS of 10.5 months, compared to 7.3 months for patients with high disease burden (n = 39), suggesting the potential for improved outcomes when treating patients in earlier lines of therapy.
Manageable Safety Profile with Predictable Adverse Events
While cytokine release syndrome (搜索) (CRS) was the most common treatment-related adverse event, occurring in 96% of patients (105/109), it was predominantly low-grade and manageable. Among patients experiencing CRS, 33% had grade 1, 55% had grade 2, and only 8% had grade ≥3 events. The onset and duration of CRS were predictable, with resolution typically occurring within one day.
Other treatment-related adverse events included diarrhea (61% all grades), nausea (55% all grades), and vomiting (53% all grades). Based on safety evaluations in later treatment cycles, the 12 mg target dose was deprioritized due to higher rates of grade ≥3 treatment-related adverse events, with 6 mg and 9 mg identified as the optimal target doses showing the best balance of safety and efficacy.
Encouraging Results in Taxane-Naive Population
Early data from the phase 1b expansion study in taxane-naive patients showed particularly promising results. Patients receiving the 6 mg weekly regimen demonstrated rapid and deep PSA reductions, with 100% of the first evaluable patients achieving PSA50 and 63% achieving PSA90 responses.
"The early data with JANX007 are highly encouraging," said Eleni Efstathiou, MD, section chief of Genitourinary Medical Oncology at Houston Methodist Cancer Center (搜索) and trial investigator. "I am deeply committed to this program and inspired by its potential to transform care for mCRPC patients, especially as its potential in earlier-line mCRPC treatment is explored."
Study Design and Patient Characteristics
The ongoing phase 1a/1b clinical trials enrolled patients 18 years and older with histologically or cytologically confirmed adenocarcinoma of the prostate (搜索). The median patient age was 68 years (range 46-86), with ECOG performance scores of 0 (n = 52) or 1 (n = 56). All patients were PSMA (搜索)-positive at baseline, with a median of 4 prior lines of therapy (range 1-9) and 89% having bone metastases.
The phase 1a portion included previously treated patients with at least 4 lines of prior therapy, while the phase 1b portion focused on patients who had not received prior taxane-based therapy for their CRPC (搜索).
Future Development Plans
David Campbell, PhD, president and chief executive officer at Janux Therapeutics, expressed optimism about the findings: "We are pleased JANX007 achieved durable responses with a manageable safety profile that compares favorably to both approved and investigational therapies in metastatic CRPC (搜索). Additionally, we found that the ability to transition patients to biweekly dosing may provide meaningful convenience advantages."
JANX007 will be evaluated as both monotherapy and in combination with darolutamide for taxane-naive, pre-Lu 177 vipivotide tetraxetan (搜索) mCRPC patients. The company also plans to evaluate JANX007 in PARP inhibitor-refractory patients as a potential route to expedited approval.