JANX007 for Prostate Cancer

Recruiting at 16 trial locations

Overseen By Janux Therapeutics

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janux Therapeutics

Disqualifiers: Organ transplant, Cardiovascular disease, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

105 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a first-in-human, Phase 1, open-label, multicenter study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and the preliminary efficacy of JANX007 administered as a single agent in adults with metastatic castration-resistant prostate cancer (mCRPC).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug JANX007 for prostate cancer?

Research on similar treatments like 177Lu-PSMA-617 shows that it can reduce tumor volume and improve survival in prostate cancer patients, especially when the cancer cells have high PSMA levels. This suggests that JANX007, which targets PSMA, might also be effective in treating prostate cancer. ^{1 2 3 4 5}

What safety data exists for PSMA-targeted therapies like JANX007 in humans?

PSMA-targeted therapies, such as 177Lu-PSMA-617, have been shown to be generally safe and well-tolerated in humans, with common side effects including dry mouth, fatigue, nausea, and diarrhea, which are manageable with standard medical care. Serious side effects were rare and included conditions like anemia and kidney injury, but these were not definitively linked to the treatment. ^{6 7 8 9 10}

What makes the drug JANX007 unique for treating prostate cancer?

JANX007, also known as PSMA-TRACTr, is unique because it targets the prostate-specific membrane antigen (PSMA) on cancer cells, potentially offering a more precise treatment for prostate cancer compared to traditional therapies. This targeted approach may help reduce damage to healthy cells and improve treatment outcomes. ^{6 11 12 13 14}

Research Team

Janux Therapeutics, MD

Principal Investigator

Janux Therapeutics

Eligibility Criteria

This trial is for adult men with metastatic castration-resistant prostate cancer who have already tried at least one novel anti-androgen therapy and a taxane regimen, or cannot take taxane due to medical reasons. They must have a PSMA expressing tumor, no significant heart disease, no organ transplants, and no active serious infections.

Inclusion Criteria

My organs are working well.

My prostate cancer was confirmed by a lab test.

I am a man aged 18 or older.

Exclusion Criteria

I do not have any serious infections.

I don't have any health issues that could affect the study's safety or results.

I have had a solid organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

IV dosing during 21- or 28-day cycles to determine the maximum tolerable dose

Varies per cohort

Expansion

IV dosing during 21- or 28-day cycles at preliminary recommended phase 2 dose (RP2D)

Varies per cohort

Backfill Expansion

IV dosing during 21- or 28-day cycles at levels previously declared tolerable

Varies per cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• JANX007

Trial Overview The study tests JANX007's safety, how well it's tolerated by the body (tolerability), its behavior in the body (pharmacokinetics), its effect on the body (pharmacodynamics), and initial effectiveness in treating advanced prostate cancer that resists standard treatments.

Participant Groups

Group I: Expansion Experimental Treatment 1 Intervention

IV dosing during 21- or 28-day cycles. Subjects will be dosed at preliminary recommended phase 2 dose (RP2D).

Group II: Dose Escalation Experimental Treatment 1 Intervention

IV dosing during 21- or 28-day cycles. Dosage per cohort will increase to determine the maximum tolerable dose.

Group III: Backfill Expansion Experimental Treatment 1 Intervention

IV dosing during 21- or 28-day cycles. Subjects will be dosed at levels previously declared tolerable.

Who Is Running the Clinical Trial?

Janux Therapeutics

Lead Sponsor

Trials

2

Recruited

240+

Findings from Research

In a study of 86 patients with castration-resistant prostate cancer (CRPC) treated with [177Lu]-Lutetium-PSMA, the median overall survival was 15 months, indicating that this treatment can be effective for some patients.

Key predictors for better survival included a pre-treatment hemoglobin level of ≥10 g/dL and lower PSA values at the start of treatment, suggesting that these factors could help identify patients who are more likely to benefit from Lu-PSMA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre. Thaiss, W., Zengerling, F., Friedrich, J., et al.[2023]

In a study involving 270 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu-PSMA), nomograms were developed to predict overall survival and PSA-progression-free survival based on various clinical and imaging factors, achieving a C-index of 0.71 for overall survival.

The nomograms effectively stratified patients into low-risk and high-risk groups, with low-risk patients showing significantly longer overall survival (24.9 months) compared to high-risk patients (7.4 months), indicating their potential utility in clinical decision-making and trial design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Gafita, A., Calais, J., Grogan, TR., et al.[2021]

In a study of 33 patients with metastatic castration-resistant prostate cancer undergoing [177Lu]-PSMA-617 therapy, baseline tumor volume (PSMA-TV) was found to be a significant predictor of overall survival (OS), indicating that larger tumor volumes at the start of treatment correlate with poorer outcomes.

Reduction in PSMA-TV after two therapy cycles did not generally predict better OS for the entire cohort; however, in patients with higher PSMA expression, a reduction in PSMA-TV was associated with improved survival, suggesting that PSMA expression levels may influence the effectiveness of tumor volume assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total tumor volume reduction and low PSMA expression in patients receiving Lu-PSMA therapy. Seifert, R., Kessel, K., Schlack, K., et al.[2022]

In a study of 52 patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing docetaxel (DTX) therapy, high PSMA-derived tumor volume (TV-PSMA) was found to significantly predict treatment failure, with patients having a TV-PSMA greater than 107 cm³ being 8.2 times more likely to experience DTX failure.

The research indicates that PSMA-based tumor burden measurements can serve as reliable predictive tools for overall survival (OS) and time to progression (TTP) in mCRPC patients, highlighting the importance of assessing tumor burden before initiating DTX therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can PSMA-based tumor burden predict response to docetaxel treatment in metastatic castration-resistant prostate cancer? Has Simsek, D., Kuyumcu, S., Karadogan, S., et al.[2021]

In a study of 56 men with metastatic castration-resistant prostate cancer treated with 177Lu-PSMA-617, 70% showed a significant PSA response, with a median PSA progression-free survival (PFS) of 8.6 months and overall survival (OS) of 22 months.

Changes in total tumor volume (TTV) measured by PSMA PET were found to be strong prognostic indicators for overall survival, with an increase in TTV by more than 30% linked to worse outcomes, highlighting the potential of posttreatment PET imaging as a valuable biomarker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Prognostic Value of Posttreatment 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in Metastatic Castration-Resistant Prostate Cancer Treated with 177Lu-PSMA-617 and NOX66 in a Phase I/II Trial (LuPIN). Pathmanandavel, S., Crumbaker, M., Nguyen, A., et al.[2023]

In a study involving 64 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 was found to be safe and well-tolerated, with manageable side effects such as dry mouth, fatigue, and nausea occurring in a significant number of patients.

The treatment did not lead to serious adverse events directly related to the drug, and there were no significant changes in vital signs or kidney function, suggesting a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). Calais, J., Czernin, J., Thin, P., et al.[2023]

PSMA-TO-1 showed greater tumor uptake than PSMA-617 in both mice and human patients, suggesting it may be more effective for targeting prostate cancer.

While PSMA-TO-1 treatment led to significantly longer survival in mice compared to PSMA-617, it also resulted in higher radiation exposure to the kidneys, indicating a need for further studies to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of PSMA-TO-1 and PSMA-617 labeled with gallium-68, lutetium-177 and actinium-225. Meyer, C., Prasad, V., Stuparu, A., et al.[2023]

A novel drug conjugate, DUPA-PTX, was developed to specifically target prostate cancer cells by utilizing the prostate-specific membrane antigen (PSMA), which is overexpressed in these cells, enhancing the delivery and efficacy of the chemotherapy drug paclitaxel (PTX).

The DUPA-PTX conjugate demonstrated strong cytotoxic effects on PSMA-expressing cancer cell lines and completely halted tumor growth without causing significant toxicity, suggesting a promising approach for targeted prostate cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen Targeted Therapy of Prostate Cancer Using a DUPA-Paclitaxel Conjugate. Lv, Q., Yang, J., Zhang, R., et al.[2019]

The new PSMA-targeting prodrug PSMA-1-VcMMAE demonstrated 48-fold greater potency in killing prostate cancer cells that express PSMA compared to those that do not, indicating its targeted efficacy.

In animal models, PSMA-1-VcMMAE significantly inhibited tumor growth and improved survival rates, while also showing a more than 10-fold improved maximum tolerated dose compared to existing treatments, suggesting a better safety profile and therapeutic index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer. Wang, X., Shirke, A., Walker, E., et al.[2021]

The new 211At-labeled radiotracer, 211At-3-Lu, effectively targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, showing significant uptake in PSMA+ tumors with minimal uptake in non-target cells, indicating its potential for targeted therapy.

In a long-term toxicity study, 211At-3-Lu demonstrated low off-target toxicity and favorable safety profiles, including stable hematopoietic function and positive histopathological outcomes, suggesting it could be a safe and effective treatment option for patients with prostate cancer resistant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Improved 211At-Labeled Agent for PSMA-Targeted α-Therapy. Mease, RC., Kang, CM., Kumar, V., et al.[2022]

The combination of 177Lu-PSMA-617 and NOX66 is a safe and feasible treatment for men with metastatic castration-resistant prostate cancer (mCRPC), with 86% of patients showing a reduction in prostate-specific antigen (PSA) levels after treatment.

Patients experienced a median overall survival of 19.7 months, and factors like higher PSMA SUVmean were linked to better treatment responses, indicating potential biomarkers for predicting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial. Pathmanandavel, S., Crumbaker, M., Yam, AO., et al.[2022]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

The LUNAR trial is investigating the efficacy of 177 Lu-PNT2002, a radiolabelled small molecule targeting prostate-specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) for men with oligorecurrent metastatic hormone-sensitive prostate cancer, with 100 patients expected to be enrolled.

This Phase 2 trial aims to determine if adding 177 Lu-PNT2002 to SBRT can improve progression-free survival and other outcomes compared to SBRT alone, potentially offering a new treatment strategy for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol). Ma, TM., Czernin, J., Felix, C., et al.[2023]

In a study involving 10 patients with low-volume metastatic hormone-sensitive prostate cancer, treatment with 177Lu-PSMA-617 was found to be safe, with no severe adverse events and all patients completing two cycles without complications.

The therapy led to significant changes in PSA levels, with half of the patients showing a response of over 50%, indicating potential effectiveness in delaying the need for androgen deprivation therapy and maintaining a good quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 in Low-Volume Hormone-Sensitive Metastatic Prostate Cancer: A Prospective Pilot Study. Privé, BM., Peters, SMB., Muselaers, CHJ., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

Total tumor volume reduction and low PSMA expression in patients receiving Lu-PSMA therapy. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Can PSMA-based tumor burden predict response to docetaxel treatment in metastatic castration-resistant prostate cancer? [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The Prognostic Value of Posttreatment 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in Metastatic Castration-Resistant Prostate Cancer Treated with 177Lu-PSMA-617 and NOX66 in a Phase I/II Trial (LuPIN). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparison of PSMA-TO-1 and PSMA-617 labeled with gallium-68, lutetium-177 and actinium-225. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen Targeted Therapy of Prostate Cancer Using a DUPA-Paclitaxel Conjugate. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

An Improved 211At-Labeled Agent for PSMA-Targeted α-Therapy. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

13. England pubmed.ncbi.nlm.nih.gov

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol). [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 in Low-Volume Hormone-Sensitive Metastatic Prostate Cancer: A Prospective Pilot Study. [2022]