Study of JANX007 in Subjects With Metastatic Castration-Resistant Prostate Cancer (ENGAGER-PSMA-01)

A Phase 1, Open-Label, Multicenter Study of JANX007 in Subjects With Metastatic Castration-Resistant Prostate Cancer

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 in adults with metastatic castration-resistant prostate cancer (mCRPC).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Metastatic Castration-resistant Prostate Cancer; Castration Resistant Prostatic Cancer
• Intervention / Treatment: Biological: JANX007; Drug: Darolutamide

• Study Type: Interventional
• Enrollment (Estimated): 272
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Janux Therapeutics; Phone Number: 858-206-8471; Email: psma-007-001_ct.gov@januxrx.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris O'Brien Lifehouse (COBLH)
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Recruiting
      • Southern Oncology Clinical Research Unit (SOCRU)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research ltd.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • University of Alabama At Birmingham Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Department of Medicine
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Helen Diller Family Comprehensive Cancer Center
      • Contact: Email: HDFCCC.CIP@ucsf.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale New Haven Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Active, not recruiting
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University Of Minnesota Medical Center
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health R.J. Zuckerberg Cancer Hospital
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Active, not recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Honickman Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male ≥18 years of age at the time of signing informed consent
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• For Dose Escalation and Backfill: Having mCRPC that progressed after at least one novel anti-androgen therapy and at least one taxane containing regimen. Participants who have actively refused a taxane containing regimen or are medically unsuitable to receive taxane are eligible
• Adequate organ function
• For Monotherapy Expansion Part a: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC setting and no more than 1 prior taxane regimen in the HSPC or CRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.
• For Monotherapy Expansion Part b: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC settings
• For Monotherapy Expansion Part d: Have received ≤ 1 anti-androgen therapy and a poly(ADP-ribose) polymerase (PARP) inhibitor for mCRPC and have progressed following treatment with the PARP inhibitor
• For Combination Expansion: Have received ≤ 1 anti-androgen therapy other than darolutamide in the HSPC setting and ≤ 1 taxane in the mCRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.

Exclusion Criteria:

• Prior solid organ transplant
• Prior treatment with PSMA-targeted CAR-T cell therapy or PSMA-CD3, PSMA-CD28 or other CD3 T-cell engaging bispecific antibodies or radioligand therapy
• Clinically significant cardiovascular disease
• For Monotherapy Expansion Part a: Prior receipt of any treatment other than an ARPI or taxane in the mCRPC setting
• For Monotherapy Expansion Part b: Prior receipt of any treatment other than an anti-androgen therapy or prior receipt of a taxane containing regimen or more than 1 prior line of therapy for mCRPC
• For Monotherapy Part d: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than an anti-androgen therapy and PARP inhibitor for mCRPC or prior receipt of a taxane in the mCRPC setting
• For Combination expansion: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than a taxane for mCRPC or prior receipt of Darolutamide or prior receipt of a taxane for HSPC
• Active clinically significant infection (bacterial, viral, fungal, mycobacteria or other)
• Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; IV dosing during 21- or 28-day cycles. Dosage per cohort will increase to determine the maximum tolerable dose.	Biological: JANX007; JANX007 is dosed via IV in a 21- or 28-day cycle.
Experimental: Backfill Expansion; IV dosing during 21- or 28-day cycles. Subjects will be dosed at levels previously declared tolerable.	Biological: JANX007; JANX007 is dosed via IV in a 21- or 28-day cycle.
Experimental: Monotherapy Expansion Parts A - D; IV dosing during 21- or 28-day cycles. Subjects will be dosed at preliminary recommended phase 2 dose (RP2D).	Biological: JANX007; JANX007 is dosed via IV in a 21- or 28-day cycle.
Experimental: Combination Expansion; IV dosing during 21- or 28-day cycles. Subjects will be dosed at preliminary recommended phase 2 dose	Biological: JANX007; JANX007 is dosed via IV in a 21- or 28-day cycle.; Drug: Darolutamide; Darolutamide is dosed via oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)	3 years
Incidence of Dose Limiting Toxicities (DLT)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who develop anti-drug antibodies against JANX007		Up to 3 years
Overall Survival	Time from treatment initiation until death from any cause	Up to 3 years
Area under the concentration time curve to infinity of JANX007 (AUC0-inf)		Pre-dose and at multiple timepoints post-dose on Days 1, 2, 4, 8, 9, 15, 16, 18 up to end of treatment (Up to 3 years)
Maximum observed concentration of JANX007 (Cmax)		Pre-dose and at multiple timepoints post-dose on Days 1, 2, 4, 8, 9, 15, 16, 18 up to end of treatment (Up to 3 years)
Duration of Response	Time from documentation of complete response or partial response to disease progression using RECIST v1.1 and PCWG3	Up to 3 years
Radiographic Progression Free Survival (rPFS)	Time from treatment initiation to radiographic evidence of disease progression using RECIST v1.1 and PCWG3	Up to 3 years
Overall Response Rate	Proportion of participants who achieve a complete response or partial response using RECIST v1.1 and PCWG3	Up to 3 years
Prostate Specific Antigen (PSA) response	Best reduction in PSA level achieved confirmed by a second PSA test ≥21 days later	Up to 3 years

Collaborators and Investigators

• Sponsor: Janux Therapeutics
• Investigators: Study Director: Janux Therapeutics, MD, Janux Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Prostate Cancer; Castration-resistant prostate cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; darolutamide
• Other Study ID Numbers: PSMA-007-001; ENGAGER-PSMA-01 (Other Identifier: Janux Therapeutics., Inc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No