San Diego-based biotech Janux Therapeutics released updated interim data from its Phase 1 clinical trial of JANX007, a first-in-class, PSMA-targeted T-cell engager developed on its TRACTr platform, in metastatic castration-resistant prostate cancer (mCRPC). The company said the data demonstrate “durable responses and a manageable safety profile,” with promising radiographic progression-free survival (rPFS) and deep prostate-specific antigen (PSA) declines in heavily pretreated patients.
Durable activity in heavily pretreated mCRPC
As of the October 15, 2025 data cut-off, a total of 109 patients had been treated across the Phase 1a dose-escalation and Phase 1b expansion cohorts.
Among RECIST-evaluable patients, 8 of 27 (≈ 30%) achieved confirmed or unconfirmed partial responses. In terms of PSA reduction, many patients achieved deep and durable declines. According to the company presentation, ≥ PSA50 (≥ 50% drop) and high fractions of PSA90 / PSA99 reductions were observed in those receiving target doses (≥ 2 mg).
Radiographic progression-free survival ranged from 7.9 to 8.9 months, including in the group switched to a less-frequent every-two-weeks (Q2W) dosing schedule, a result Janux says compares favorably with existing mCRPC therapeutic benchmarks.
Safety remains a key challenge for T-cell engagers in solid tumors, particularly cytokine release syndrome (CRS). Janux reported that CRS events were largely limited to Grades 1 and 2 and mainly occurred in the first treatment cycle. The company has identified a mitigation strategy that kept the safety profile manageable.
Based on these findings, Janux sees a Q2W dosing interval as a viable and more convenient regimen for patients, something that could be especially valuable for those with advanced disease.
Earlier-line and combination therapy plans
Janux’s leadership emphasised the potential of JANX007 not just in late-stage, heavily treated mCRPC, but also earlier in the disease course. “We look forward to evaluating the potential for JANX007 in earlier-line mCRPC, where improved tolerability and durability could have an even greater impact,” said CEO David Campbell.
The company is now planning further development of JANX007 both as monotherapy and in combination with androgen receptor inhibitors for taxane-naïve mCRPC patients. They are also evaluating use in PARP-inhibitor–refractory patients, potentially accelerating the path to registration if results continue to be supportive.
Significance for PSMA-targeted therapies
PSMA-targeting has become a validated approach in prostate cancer, for example, with radioligand therapies. The benchmark is set by Novartis with ^177Lu-PSMA-617 (Pluvicto), a radioligand therapy approved for mCRPC, while Telix Pharmaceuticals: is developing TLX591 (radiolabeled antibody) and TLX591-CDx (imaging agent), and Bayer is also involved in the development of PSMA-targeted alpha therapies.
T-cell engagers in this space have historically encountered toxicity or insufficient solid-tumor efficacy. Janux’s “tumour-activated” TRACTr design attempts to address these issues by minimizing off-tumor effects and toxicity in healthy tissues. The challenge for Janux in differentiating JANX007 from the competition will now focus on earlier-line disease.