Immunotherapies show safety and efficacy in mCRPC, renal cell carcinoma

Positive updated clinical data underscore the safety and efficacy of PSMAxCD3-TRACTr JANX007 for the treatment of patients with metastatic-castration resistant prostate cancer (mCRPC) and EGFRxCD3-TRACTr JANX008 for the treatment of patients with advanced solid tumors, including renal cell carcinoma (RCC), announced Janux Therapeutics in a news release.¹

Janux expects to provide an update on doses for expansion for JANX007 in the second half of 2024.

Both therapies utilize Janux’s Tumor Activated T Cell Engager (TRACTr) platform.

“These clinical data show encouraging safety and efficacy with JANX007 in metastatic castration-resistant prostate cancer and with JANX008 in late-stage solid tumors. The clinical data provide compelling proof-of-concept for the TRACTr platform in a setting where many other approaches have failed due to material safety issues or lack of efficacy,” said David Campbell, PhD, president and CEO of Janux Therapeutics, in the news release.¹ “Our TRACTr platform provides an entry point to multiple, large solid tumor indications that are intractable with conventional TCE approaches. We look forward to continuing to advance these clinical trials and expanding to additional TCE targets, as we look to fulfill our mission to meaningfully address the unmet medical needs for cancer patients, especially those with late-stage disease.”

Data on PSMAxCD3-TRACTr JANX007

JANX007, designed to target prostate-specific membrane antigen (PSMA), is being explored in the phase 1a ENGAGER-PSMA-01 clinical trial (NCT05519449). The study is assessing the safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy of the therapy in patients with mCRPC.

In total, 23 patients were treated in the dose-escalation study as of the data cut-off of February 12, 2024.

At the lowest dose level of 0.1 mg or above, 78% (14 of 18) of patients achieved a PSA decline of at least 30%, and 56% (10 of 18) of patients achieved a PSA decline of at least 50%. At the dose level of 0.2 mg or above, 100% (6 of 6) of patients achieved a PSA decline of at least 30%, and 83% (5 of 6) achieved a PSA decline of at least 50%. One patient in this cohort achieved a PSA decline of at least 90%.

Regarding safety, incidences of Cytokine Release Syndrome (CRS) were reported, though they were observed to temporary and mild as low-grade 1 or 2 events. Incidents of CRS were mainly reported during the first treatment cycle and were quickly managed with treatment, according to the news release.

The majority of treatment-related adverse events (TRAEs) not associated with CRS tended to be grade 1 or 2 and primarily occurred in the initial treatment cycle. The incidence of grade 3 TRAEs were low. No grade 4 or 5 TRAEs were reported.

Treatment with PSMAxCD3-TRACTr JANX007 has been administered in doses up to 3 mg, which has exceeded the anticipated maximum tolerable dose for the parental T cell engager. The maximum tolerable dose for the TRACTr has not yet been established.

Janux expects to provide an update on doses for expansion in the second half of 2024.

Data on EGFRxCD3-TRACTr JANX008

A phase 1 clinical trial (NCT05783622) is also exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of JANX008 in patients with advanced solid tumors. JANX008 is designed to target the epidermal growth factor receptor (EGFR).

In total, 11 patients were treated in the dose-escalation study as of the data cut-off of February 12, 2024. The study included patients with RCC, as well as those with colorectal cancer, squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC).

At the 0.15 mg once-weekly dose level, 1 patient with RCC experienced a 12% reduction in the size of a large RCC mass and significant clinical benefit. The patient experienced grade 1 CRS. Additionally, at that dose level, 1 patient with NSCLC experienced a partial response as defined by RECIST criteria, a 100% reduction of the target lung lesion, and elimination of liver metastasis. No CRS or TREAs were reported. The patient remains on treatment and their partial response has been maintained through their scan at week 18.

Patients included in the study have been treated at a dose level up to 1.25 mg, which is significantly above the projected maximum tolerable dose for the parental T cell engager. At that dose level, 2 patients experienced grade 1 CRS, and no grade 2 or higher CRS was observed. The majority of TRAEs not related to CRS also tended to be grade 1 or 2 and occurred predominately in the initial treatment cycle. No patients have reported serious TRAEs or any dose-limiting toxicities.

The dose escalation and optimization portion of the trial remains ongoing.

Reference

1. Janux announces encouraging safety and efficacy data in ongoing dose escalation trials for PSMAxCD3-TRACTr JANX007 in mCRPC and EGFRxCD3-TRACTr JANX008 in solid tumors. News release. Janux. Published online February 26, 2024. Accessed Febraury 27, 2024. https://investors.januxrx.com/investor-media/news/news-details/2024/Janux-Announces-Encouraging-Safety-and-Efficacy-Data-in-Ongoing-Dose-Escalation-Trials-for-PSMAxCD3-TRACTr-JANX007-in-mCRPC-and-EGFRxCD3-TRACTr-JANX008-in-Solid-Tumors/default.aspx