JANX007 demonstrates encouraging clinical activity in mCRPC

Updated data from the phase 1a ENGAGER-PSMA-01 trial (NCT05519449) showed safety and encouraging anti-tumor activity of the PSMA-targeting TRACTr JANX007 in the treatment of patients with metastatic-castration resistant prostate cancer (mCRPC), Janux Therapeutics announced in a news release.¹

Janux expects to provide another update in 2025.

Based on these results, the investigators have selected 2 once-weekly step dose regimens for further investigation in the phase 1b expansion trial in patients who have not yet received lutetium Lu 177 vipivotide tetraxetan (Pluvicto) as their second- or third-line treatment.

“These clinical data show substantial activity with JANX007 in 5L [mCRPC] patients and provide compelling support for the doses we’ve selected for expansion trials directed at pre-PLUVICTO 2L and 3L patients,” said David Campbell, PhD, president and CEO of Janux Therapeutics, in the news release.¹ “We look forward to rapidly advancing JANX007 into second and third-line therapy where a substantial unmet need remains and where we believe JANX007’s highly differentiated profile could allow for broad usage, if approved. This is an exciting day for Janux, but more importantly the prostate cancer patients we serve.”

Overall, the ENGAGER-PSMA-01 study is assessing the safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy of JANX007 monotherapy in patients with mCRPC.

As of the data cutoff date of November 15, 2024, 16 pre-PLUVICTO patients were treated in the study. Each patient received once-weekly target doses ranging from 2 mg to 9 mg via IV in a 21- or 28-day cycle. Participants enrolled had a median of 4 prior lines of therapy.

Data showed that 100% of patients achieved a prostate-specific antigen (PSA) decline of at least 50% (PSA50), 63% of patients achieved a PSA decline of at least 90% (PSA90), and 31% of patients achieved a PSA decline of at least 99%. At target doses of 2 mg or higher, 75% of patients maintained a PSA50 decline and 50% maintained a PSA90 decline for 12 weeks or more.

According to the company, “Deep and durable PSA responses were observed irrespective of resistance driver aberration status, or prior treatments with a taxane or ARPi.”

Additionally, 50% (4 of 8) of RECIST-evaluable patients achieved a confirmed or unconfirmed partial response. The disease control rate was 63% (5 of 8 patients).

Regarding safety, JANX007 was generally well-tolerated. Cytokine release syndrome (CRS), CRS-related adverse events, and treatment-related adverse events not associated with CRS were generally grade 1 and 2 and primarily occurred in the first treatment cycle. The maximum tolerable dose for the TRACTr had not yet been established at the time of data report.

In total, the open-label phase 1 study plans to enroll 105 adult patients across 16 clinical trial sites in the US and Australia.²

To be eligible for enrollment, patients need to have histologically or cytologically confirmed adenocarcinoma of the prostate, mCRPC that progressed following at least 1 novel anti-androgen therapy and at least 1 taxane-containing regimen, and adequate organ function.

The primary outcome measures are the incidence of dose-limiting toxicities, adverse events, and serious adverse events. Secondary outcome measures include overall response rate, PSA response, duration of response, radiographic progression-free survival, and overall survival.

Janux expects to provide additional updated data from the trial in 2025. Final completion of the study is anticipated for December 2026.

References

1. Janux announces doses selected for phase 1b expansion trials supported by encouraging efficacy and safety profile observed in phase 1a dose escalation for JANX007 in mCRPC. News release. Janux Therapeutics. December 2, 2024. Accessed December 3, 2024. https://www.businesswire.com/news/home/20241202674893/en/Janux-Announces-Doses-Selected-for-Phase-1b-Expansion-Trials-Supported-by-Encouraging-Efficacy-and-Safety-Profile-Observed-in-Phase-1a-Dose-Escalation-for-JANX007-in-mCRPC

2. Study of JANX007 in subjects with metastatic castration-resistant prostate cancer (ENGAGER-PSMA-01). ClinicalTrials.gov. Last updated September 23, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT05519449