Janux Therapeutics has initiated Phase 1b expansion studies for its lead immunotherapy candidate JANX007 in patients with metastatic castration-resistant prostate cancer (mCRPC), following encouraging results from earlier clinical testing.
The San Diego-based biopharmaceutical company announced today that the first Phase 1b expansion study will focus on taxane-naïve mCRPC patients who have progressed on or after novel hormonal therapy (NHT). This study represents a strategic move to evaluate JANX007 in earlier treatment lines, specifically first and second-line patient populations.
Promising Phase 1a Results Support Expansion
Updated data from the Phase 1a dose escalation portion of the ENGAGER-PSMA-01 trial revealed a median radiographic progression-free survival (rPFS) of 7.5 months across all 16 heavily pre-treated patients who had received a median of four prior lines of therapy. Notably, patients treated at the higher 6mg and 9mg target doses (n=9) achieved an improved median rPFS of 7.9 months.
The 6-month rPFS rate was 65% for all patients and increased to 78% for those receiving the higher doses. Safety data remained consistent with previous disclosures from December 2024.
"Initiation of the taxane-naïve study marks an important step as we begin to evaluate JANX007 in earlier-line mCRPC patient populations," said Zachariah McIver, D.O., Ph.D., Chief Medical Officer of Janux. "While therapeutic options for mCRPC have expanded, there remains a significant need for novel, non-chemotherapeutic approaches."
Expansion Study Design and Dosing Strategy
The Phase 1b expansion study will assess JANX007 monotherapy at two dose regimens (0.3/2/6mg and 0.3/2/9mg), with dosing administered either weekly or biweekly. The company has also implemented a cytokine release syndrome (CRS) mitigation strategy designed to maintain the favorable CRS profile reported in December.
ENGAGER-PSMA-01 is a first-in-human, open-label, multicenter Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of JANX007 administered as monotherapy or in combination therapy.
Comprehensive Development Program
Beyond the taxane-naïve study, Janux plans to initiate three additional Phase 1b expansion studies:
- JANX007 in combination with an androgen receptor inhibitor in taxane-experienced mCRPC patients
- JANX007 monotherapy in PARP inhibitor-resistant mCRPC patients
- JANX007 monotherapy in NHT- and taxane-experienced mCRPC patients to support OPTIMUS dose selection for registrational studies
David Campbell, Ph.D., President and CEO of Janux, explained the rationale for moving to earlier treatment lines: "Improved efficacy and durability of responses has been observed by other prostate cancer drugs and TCEs when moving into earlier lines of therapy. There are also indications that safety with TCEs improve in earlier lines of therapy where disease burden is lower. We believe that these observations, coupled with the data seen in our Phase 1a dose escalation in later line patients, strongly support our decision to develop JANX007 in earlier lines of therapy."
Innovative Platform Technology
JANX007 is a Tumor Activated T Cell Engager (TRACTr) that targets prostate-specific membrane antigen (PSMA). The TRACTr platform is designed to activate T cells only in the tumor microenvironment, potentially improving safety and efficacy compared to conventional T cell engagers.
The company's proprietary technology has enabled the development of two distinct bispecific platforms: TRACTr and Tumor Activated Immunomodulator (TRACIr). Both platforms aim to provide cancer patients with therapeutics that direct the immune system to eradicate tumors while minimizing safety concerns.
Pipeline and Future Developments
In addition to JANX007, Janux is advancing JANX008, a TRACTr targeting epidermal growth factor receptor (EGFR) for multiple solid tumors including colorectal carcinoma, head and neck squamous cell carcinoma, and various other cancers.
The company plans to present additional data from both JANX007 and JANX008 in the second half of 2025. Janux will also host an R&D Day in mid-2025 to highlight product candidates from its preclinical pipeline that are advancing toward clinical trials.
For patients with mCRPC, these developments represent potential new treatment options in a disease area where novel, non-chemotherapeutic approaches are urgently needed despite recent therapeutic advances.
