Sophic Logo gordian knotProstate Cancer Clinical Trials Intelligence

Monthly Update Report - October 2025


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Important Notice:
Sophic does not practice medicine nor provide medical advice. The Sophic Starlight Cancer Clinical Trials Intelligence Report is intended solely as an educational resource that provides access to publicly available clinical trial data integrated within Sophic’s proprietary knowledgebase and summarized with AI. This report is not a substitute for professional medical advice, diagnosis, or treatment.

1: Summary data from new trials identified for Prostate Cancer.


Overview

Number of Trials: 14

These 14 trials focus on advanced and metastatic prostate cancer, including castration-resistant (mCRPC), hormone-sensitive (mHSPC), and neuroendocrine variants. Most trials test novel targeted therapies, radioligand therapies, and combination regimens. Common themes include androgen receptor pathway inhibition, PARP inhibition, DLL3-targeted radioligands, PSMA-targeted imaging and therapy, and immune-oncology approaches. Several trials explore biomarker-driven enrollment (e.g., HRR mutations, DLL3 expression, PSMA uptake). Exercise intervention and focal therapy monitoring are also represented.

Common Criteria Across Trials

Common Inclusion

  • Histologically confirmed prostate adenocarcinoma
  • Age ≥18 years
  • ECOG performance status 0–2
  • Metastatic disease documented by imaging (bone scan, CT, MRI, or PSMA PET)
  • Castrate testosterone level <50 ng/dL
  • Progressive disease (PSA progression, radiographic progression, or both)
  • Prior androgen receptor pathway inhibitor (abiraterone, enzalutamide, darolutamide, apalutamide)
  • Adequate organ function (bone marrow, renal, hepatic)
  • Life expectancy ≥6–12 months
  • Willingness to use contraception

Common Exclusion

  • Small cell or pure neuroendocrine carcinoma (except in neuroendocrine-specific trials)
  • Untreated or symptomatic brain metastases
  • Uncontrolled cardiovascular disease or recent myocardial infarction
  • Active uncontrolled infection (including HIV, HBV, HCV)
  • Prior treatment with the investigational agent class (e.g., prior PARP inhibitor, prior DLL3-targeted therapy)
  • Unresolved toxicity from prior therapy >Grade 1
  • Concurrent strong CYP3A4 or CYP2C8 inducers/inhibitors
  • History of seizure or conditions predisposing to seizure
  • Other active malignancy requiring treatment
  • Spinal cord compression or leptomeningeal disease (unless treated and stable)

Outcomes Summary

Primary Outcomes

Secondary Outcomes


2: Extracted Trials with New Information


Trials with Special Criteria

Genomic / Biomarker Trials

Unique or Unusual Criteria

Trials with Emerging Treatments


3: Individual Trial Overviews


NCT06165302

EPC Trial: Exercise in Prostate Cancer Genomic-based

Organization/Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins


Example patient: A 72-year-old man with metastatic prostate adenocarcinoma on abiraterone for 6 months with rising PSA and AR-V7 positive CTCs, ECOG 1, without severe bone pain or fracture risk.

Phase N/A

Interventions

  • Behavioral: Exercise Intervention
    Summary: A program of managed physical activity to improve an individual's health and wellbeing (NCI Thesaurus).

Key Inclusion

  • Metastatic prostate adenocarcinoma
  • Currently on androgen deprivation therapy for at least 3 months
  • Elevated PSA >1ng/mL or rising PSA
  • CTC positive by AR-V7 testing
  • ECOG performance status ≤1
  • Age ≤80 years

Key Exclusion

  • Small cell carcinoma of the prostate
  • Impaired cognition limiting exercise participation
  • Moderate to severe bone pain limiting activities of daily living
  • Clinical progression requiring systemic therapy change
  • Bone metastases requiring radiation or surgery for fracture risk
  • Significant cardiovascular disease making exercise unsafe
  • Major surgery within past 4 weeks

NCT07006727

A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors

Organization/Sponsor: Novartis


Example patient: A 62-year-old man with metastatic small cell lung cancer progressing after two lines of platinum-based chemotherapy, with adequate bone marrow and renal function, no CNS metastases, and QTcF of 440 msec.

Phase I

Interventions

  • Radioligand Therapy: 111In-ETN029
    Summary: DLL3-targeting radioligand therapy delivering radioactive indium-111 to DLL3-expressing tumors for imaging and dosimetry assessment in lung cancer (Summary of Web Search).
  • Radioligand Therapy: 225Ac-ETN029
    Summary: DLL3-targeting radioligand therapy using actinium-225 alpha-particle radiation to destroy DLL3-expressing cancer cells in lung and neuroendocrine tumors (Summary of Web Search).

Key Inclusion

  • Age ≥ 18 years old
  • Locally advanced, unresectable, or metastatic SCLC with progression after ≥1 line including platinum chemotherapy
  • LCNEC of lung with progression after ≥1 line including platinum chemotherapy (dose escalation only)
  • Castration-resistant or de novo NEPC with neuroendocrine markers confirmed by IHC (dose expansion only)
  • GEP-NEC with progression after ≥1 line including platinum chemotherapy (dose expansion only)
  • Measurable lesion with 111In-ETN029 uptake on SPECT/CT (NEPC and GEP-NEC expansion cohorts)
  • No more than 2 prior lines of systemic therapy (dose expansion)
  • Prior DLL3-targeted therapy allowed for SCLC; prior Lu-177 PSMA RLT allowed for NEPC

Key Exclusion

  • ANC < 1.0 x 10^9/L, hemoglobin < 9 g/dL, or platelets < 75 x 10^9/L
  • QTcF ≥ 470 msec
  • eGFR < 60 mL/min
  • Unmanageable urinary tract obstruction or incontinence
  • Leptomeningeal disease or symptomatic CNS metastases requiring local therapy
  • History of or current interstitial lung disease or pneumonitis ≥ Grade 2
  • Prior DLL3-targeted therapy (except SCLC) or prior RLT (except NEPC)

NCT06844383

A Randomized Open-label Phase 2 Study of TALazoparib With or Without ENzaluTamide in Patients With Metastatic Castration-Resistant Prostate Cancer and HRR Mutations After Progression on Abiraterone Acetate Genomic-based

Organization/Sponsor: Prostate Cancer Clinical Trials Consortium


Example patient: A 67-year-old man with metastatic castration-resistant prostate cancer harboring a germline BRCA2 mutation, ECOG status 1, testosterone 25 ng/dL on continuous LHRH agonist, who progressed on abiraterone with rising PSA and new bone metastases, with no prior PARP inhibitor or platinum chemotherapy exposure.

Phase 2

Interventions

  • Drug: Talazoparib
    Summary: Talazoparib is an orally bioavailable PARP inhibitor that prevents DNA repair of single-strand breaks via base-excision repair, leading to genomic instability and apoptosis in tumors with deficient homologous recombination repair. FDA-approved for HRR gene-mutated metastatic castration-resistant prostate cancer in combination with enzalutamide and germline BRCA-mutated HER2-negative breast cancer. Source: FDA label, NCI Thesaurus.
  • Drug: Talazoparib with enzalutamide
    Summary: Combination regimen of talazoparib (PARP inhibitor) and enzalutamide (androgen receptor inhibitor) for prostate cancer treatment. Enzalutamide inhibits androgen receptor signaling and acts as a CYP450 inducer (2C9, 2C19, 3A4), requiring monitoring for drug-drug interactions. FDA-approved for various prostate cancer settings including castration-resistant and castration-sensitive disease. Source: FDA label, NCI Thesaurus.

Key Inclusion

  • Metastatic castration-resistant prostate cancer with pathogenic HRR mutation (BRCA1, BRCA2, ATM, CDK12, CHEK2, PALB2, MLH1, NBN, ATR, FANCA, MRE11A, RAD51C)
  • Prior abiraterone acetate with prednisone for mHSPC or locally advanced disease with progression
  • Progressive disease with rising PSA, soft tissue progression, bone progression, or new PSMA PET lesions
  • Testosterone levels <50 ng/dL with surgical or medical castration
  • ECOG performance status ≤1
  • Age ≥18 years
  • Adequate organ function including ANC ≥1500/µl, hemoglobin ≥9g/dl, platelets ≥100,000/µl
  • Willing to remain on study treatment despite PSA progression unless clinically deteriorating

Key Exclusion

  • Prior treatment with PARP inhibitor
  • Prior ARPI other than abiraterone acetate for ≥12 weeks in CRPC setting
  • Prior platinum-based chemotherapy for prostate cancer
  • Chemotherapy for castration-sensitive disease within 6 months
  • Current use of potent P-gp inhibitors or strong CYP2C8 inhibitors/inducers within 7 days
  • History of seizure or conditions predisposing to seizure
  • Untreated brain metastases or spinal cord compression
  • Grade >2 treatment-related toxicity from prior therapy except alopecia or peripheral neuropathy

NCT06941480

Characterizing the Theranostic Potential of DLL3-targeting Agents in High-grade Neuroendocrine Carcinomas of the Lung and Prostate Genomic-based

Organization/Sponsor: Memorial Sloan Kettering Cancer Center


Example patient: A 62-year-old man with metastatic neuroendocrine prostate cancer with RB1 and TP53 mutations, PSA 8 ng/mL with 25 bone lesions, progressing after platinum-based chemotherapy, ECOG 1, with DLL3-positive tumors on biopsy.

Phase N/A

Interventions

  • Radioligand Therapy: 177Lu-DTPA-SC16.56
    Summary: Lutetium-177 labeled antibody targeting DLL3 protein for radioligand therapy in small-cell lung cancer and neuroendocrine prostate cancer, delivering radiation to kill cancer cells (Web Search).
  • Diagnostic Imaging: PET/CT
    Summary: Positron emission tomography combined with computed tomography using radioactive tracer for cancer detection, staging, tumor localization, and treatment monitoring (Web Search).

Key Inclusion

  • Histologically proven progressive metastatic high-grade neuroendocrine carcinomas of lung or prostate
  • Relapsed following at least 1 line of standard chemotherapy
  • DLL3 overexpression with SUVmax greater than normal liver in ≥80% of progressing lesions ≥2cm
  • At least one tumor lesion ≥2cm on CT or MR
  • ECOG performance status 0 to 2
  • Disease progression within 3 months of study entry
  • Adequate hematologic, renal, and hepatic function
  • Willingness to undergo baseline and follow-up biopsy

Key Exclusion

  • Prior treatment with Rova-T (rovalpituzumab)
  • History of anaphylactic reaction to humanized or human antibodies
  • Uncontrolled brain metastases or carcinomatous meningitis
  • Unmanageable urinary incontinence
  • Concurrent chemotherapy, other radiopharmaceuticals, or immunotherapy
  • Life expectancy less than 6 months
  • Major surgery within 28 days
  • Metastatic disease exclusively evident by PSMA PET

NCT07185165

Eclipse: Flotufolastat F 18 to Determine Treatment Success Following Prostate Focal Therapy

Organization/Sponsor: Jonsson Comprehensive Cancer Center


Example patient: A 62-year-old man with prostate cancer who underwent HIFU focal therapy 12 months ago, now requiring imaging assessment for treatment success without current androgen deprivation therapy.

Phase N/A

Interventions

  • Procedure: Ultrasound-Guided Prostate Biopsy
    Summary: Diagnostic procedure using real-time ultrasound imaging to obtain tissue samples from suspicious prostate areas via transrectal or transperineal approaches for cancer diagnosis (Web Search).
  • Diagnostic Test: Positron Emission Tomography
    Summary: Imaging technique detecting gamma radiation from positron-electron collisions to assess metabolic activity and guide cancer therapy monitoring (NCI Thesaurus).
  • Drug: Fluorine F 18 Flotufolastat
    Summary: Radioactive diagnostic agent targeting PSMA-positive prostate cancer lesions for PET imaging, using fluorine-18 decay to produce gamma photons for detecting metastasis or recurrence (FDA label, NCI Thesaurus).
  • Diagnostic Test: Computed Tomography
    Summary: X-ray imaging method using computer reconstruction to create cross-sectional body scans for monitoring disease progression (NCI Thesaurus).

Key Inclusion

  • Men aged 18-90 years
  • History of prostate cancer
  • Prior focal therapy within 6-36 months
  • Focal therapy types: laser, cryotherapy, HIFU, Tulsa Pro, IRE, or brachytherapy

Key Exclusion

  • Contraindication to flotufolastat F 18 PET CT
  • Contraindication to ultrasound-guided prostate biopsy
  • X-ray contrast or PET radiotracer within 24 hours of scan
  • Castrate testosterone levels from androgen deprivation therapy
  • Inability to lie still for 30 minutes
  • Investigational agents within 42 days
  • Severe claustrophobia or inability to maintain raised arms position

NCT07206056

TulmiSTAR-01: A Two-part, Phase I Dose Escalation and Expansion Followed by a Randomized, Open-label Multicenter, Phase II Study to Assess the Safety and Efficacy of the Combination of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) vs Standard of Care in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer

Organization/Sponsor: Novartis


Example patient: A 67-year-old man with metastatic castration-resistant prostate adenocarcinoma, castrate testosterone levels, bone metastases on imaging, and disease progression after enzalutamide treatment, who has not received taxane chemotherapy in the mCRPC setting.

Phase 1, Phase 2

Interventions

  • Drug: Tulmimetostat
    Summary: Oral selective EZH2 inhibitor that prevents histone H3K27 methylation, altering gene expression to decrease proliferation in EZH2-expressing cancer cells; used for antineoplastic activity (NCI Thesaurus).
  • Drug: Luxdegalutamide
    Summary: Oral AR-targeted PROTAC protein degrader that recruits E3 ligase to ubiquitinate and degrade AR, halting AR-mediated signaling and inhibiting CRPC cell proliferation including resistance mutations like L702H (NCI Thesaurus).
  • Other: Standard of Care
    Summary: Standard treatment protocol requiring formal clarification per ICH M11 guidelines (NCI Thesaurus).

Key Inclusion

  • Adult men ≥18 years with histologically confirmed prostate adenocarcinoma without neuroendocrine or small cell features
  • ≥1 metastatic lesion on CT, MRI, or bone scan within 28 days prior to treatment start
  • Progressive metastatic castration-resistant prostate cancer (mCRPC)
  • Castrate serum testosterone level <50 ng/dL or <1.7 nmol/L
  • Progressed on at least one prior second-generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide)
  • Part 1a: ≤2 prior chemotherapy lines in CRPC setting permitted
  • Part 1b: up to one prior chemotherapy line in CRPC setting permitted
  • Part 2: taxane-naïve in mCRPC setting, prior chemotherapy only in HSPC setting

Key Exclusion

  • Previous treatment with PRC2 inhibitors including EZH2, EZH2/1, or EED inhibitors
  • Previous treatment with AR-targeting protein degrader compounds
  • Known hypersensitivity or contraindication to study treatment components
  • Investigational agent within 28 days or 5 half-lives prior to study entry
  • Radioligand therapy in mCRPC setting (except Part 1a)
  • Biochemical recurrence or PSA-only disease without metastases and normal PSA ≥1 year
  • Untreated or unstable CNS metastases requiring corticosteroids for neurologic integrity
  • Active leptomeningeal disease with neurological impairment

NCT07011342

Utility of 18F-rhPSMA-7.3 in the Diagnosis of Prostate Cancer After Focal Gland Treatment

Organization/Sponsor: Hackensack Meridian Health


Example patient: A 62-year-old man with intermediate-risk prostate cancer who underwent focal cryoablation 6 months ago, has a life expectancy over 10 years, and completed pre-treatment MRI and standard template biopsy.

Phase N/A

Interventions

  • Diagnostic: 18F-rhPSMA-7.3
    Summary: A radiohybrid PSMA ligand labeled with fluorine F-18 for PET/CT or PET/MRI imaging that targets PSMA-expressing prostate cancer cells; PSMA is overexpressed in prostate cancer and increases with tumor differentiation and hormone-refractory disease (Source: NCI Thesaurus).

Key Inclusion

  • Adult males 18 years or older
  • Pre-treatment MRI required
  • Underwent focal therapy or hemiablation within past 9 months
  • Intermediate risk prostate cancer per AUA/NCCN guidelines
  • Life expectancy of 10 years or more
  • Standard template biopsy with minimum 2 cores into MRI visible lesion
  • Ability to provide informed consent
  • Ability to adhere to study visits and specimen collection

Key Exclusion

  • Patients under age 18
  • Prior whole gland ablation
  • Prior partial gland ablation over 9 months before enrollment

NCT07189403

A Phase 1, First-in-human (FIH), Multicenter, Open-label Trial of DS9051b in Participants With Advanced or Metastatic Adrenocortical Carcinoma (ACC) and Metastatic Castration-resistant Prostate Cancer (mCRPC)

Organization/Sponsor: Daiichi Sankyo


Example patient: A 67-year-old man with metastatic castration-resistant prostate cancer, ECOG PS 1, previously treated with abiraterone for 18 months and one line of docetaxel chemotherapy, now with PSA progression and adequate organ function.

Phase 1

Interventions

  • Drug: DS9051b
    Summary: DS9051b targets specific pathways for treating metastatic castration-resistant prostate cancer; exact mechanisms undisclosed; studied for safety and efficacy in initial trials (Source: Web Search).

Key Inclusion

  • Adults ≥18 years of age
  • Histologically confirmed adenocarcinoma of the prostate or ACC
  • ECOG PS of 0, 1, or 2 due to cancer pain
  • mCRPC with at least 1 line of ARPI therapy for minimum 12 weeks
  • At least 1 line of chemotherapy or ineligibility/refusal of chemotherapy
  • Documented disease progression by PSA, soft tissue, or bone criteria
  • Adequate organ and bone marrow function

Key Exclusion

  • History of pituitary gland dysfunction
  • Active or uncontrolled autoimmune disease requiring systemic treatment
  • Systemic corticosteroid >5 mg prednisone or >100 μg fludrocortisone daily equivalent
  • Spinal cord compression or clinically active CNS metastases
  • Uncontrolled or significant cardiovascular disease
  • History of another primary malignancy within 3 years except specified exceptions
  • Unresolved toxicities from prior anticancer therapy >Grade 1
  • Known GI disease interfering with absorption including PPI/antacid use

NCT07103018

Phase 1, Dose-Escalation Study of KTX2001 (an NSD2 Inhibitor) Alone and in Combination With Darolutamide for Metastatic Castration-Resistant Prostate Cancer

Organization/Sponsor: K36 Therapeutics, Inc.


Example patient: A 67-year-old male with ECOG 1, metastatic castration-resistant prostate cancer with bone and lymph node metastases on CT, who progressed after enzalutamide treatment, with adequate organ function and no brain metastases.

Phase 1

Interventions

  • Drug: KTX-2001
    Summary: KTX-2001 is a selective NSD2 inhibitor that targets H3K36me2 to silence oncogenic programs in metastatic castration-resistant prostate cancer (source: Web Search).
  • Drug: KTX-2001 + Darolutamide (NUBEQA)
    Summary: Darolutamide is an androgen receptor inhibitor that prevents AR activation and nuclear translocation, inhibiting transcription of genes regulating prostate cancer cell proliferation (source: FDA label, NCI Thesaurus).

Key Inclusion

  • Age ≥18 years
  • ECOG score 0 or 1
  • Male with metastatic castration-resistant prostate cancer per PCWG3 criteria
  • Metastatic disease documented by bone scan, CT, or MRI
  • Progressed on or after androgen receptor pathway inhibitor (abiraterone, enzalutamide, darolutamide, or apalutamide)
  • Adequate renal function (creatinine clearance >50 mL/min)
  • Adequate hepatic function (bilirubin ≤1.5× ULN, AST/ALT ≤2.5× ULN)
  • Adequate hematological function (neutrophils >1×10⁹/L, platelets >100×10⁹/L, hemoglobin >9 g/dL)

Key Exclusion

  • Symptomatic or uncontrolled brain metastases or leptomeningeal disease
  • Symptomatic or impending untreated cord compression
  • Drug-related toxicity from prior therapy not resolved to Grade ≤1 (except alopecia, Grade 2 neuropathy)
  • Active uncontrolled infection including HBV, HCV, HIV with detectable viral load
  • QTcF >470 msec or unstable cardiovascular function
  • Strong CYP3A inducers or inhibitors within 10 days or 5 half-lives
  • Anticancer therapy within 2 weeks (4 weeks for chemotherapy or radioligand therapy)
  • Herbal products or alternative therapies that may decrease PSA within 4 weeks

NCT07145177

A Phase 1b Study of 177Lu-PSMA-617 Combined With Liver Directed Therapy in Metastatic Castration Resistant Prostate Cancer

Organization/Sponsor: University of California, San Francisco


Example patient: A 68-year-old man with metastatic castration-resistant prostate cancer progressing on enzalutamide with castrate testosterone levels, ECOG status 1, multiple PSMA-avid bone metastases and three liver metastases amenable to TACE, who previously received one line of docetaxel chemotherapy.

Phase 1

Interventions

  • Radioligand Therapy: 177Lu-PSMA-617
    Summary: Radioligand targeting prostate-specific membrane antigen (PSMA) on prostate cancer cells, delivering radioactive lutetium-177 to kill cancer cells; FDA-approved for metastatic castration-resistant prostate cancer (Summary of Web Search).
  • Procedure: Trans-arterial chemoembolization (TACE)
    Summary: Minimally invasive liver-directed therapy blocking blood flow to tumors and delivering chemotherapy directly; commonly used for liver metastases to shrink tumors by starving them of blood (Summary of Web Search).
  • Procedure: Ablation
    Summary: Energy-based treatment using heat, cold, or electricity to destroy cancerous tissue; aims to reduce side effects compared to traditional treatments (Summary of Web Search).
  • Diagnostic Test: Positron Emission Tomography (PET)/Computerized tomography (CT)
    Summary: Combined imaging technique using radiotracers to detect PSMA-positive lesions and metabolic activity; used for staging and restaging prostate cancer (Summary of Web Search).
  • Procedure: Tumor Biopsy
    Summary: Tissue sampling procedure using imaging guidance to obtain prostate or metastatic tissue for cancer diagnosis and molecular analysis (Summary of Web Search).
  • Other: Questionnaire
    Summary: EORTC QLQ-PR25 self-reporting tool measuring patient-reported outcomes and quality of life specific to prostate cancer symptoms and functional issues (Summary of Web Search).

Key Inclusion

  • Histologically confirmed prostate cancer with progressive disease by PCWG3 criteria
  • Castrate testosterone level (<50 ng/dL) maintained on LHRH analogue if no orchiectomy
  • Prior progression on at least one second generation androgen signaling inhibitor (abiraterone, apalutamide, darolutamide, or enzalutamide)
  • At least one PSMA-avid extrahepatic lesion on screening PSMA PET
  • One or more liver metastases amenable to liver-directed therapy
  • ECOG performance status ≤2 or Karnofsky ≥50%
  • Adequate organ function including platelets ≥100,000/mcL and creatinine clearance ≥30 mL/min
  • Availability of archival mCRPC tissue or willingness to undergo fresh biopsy

Key Exclusion

  • De novo small cell neuroendocrine prostate cancer
  • Prior PSMA-directed radioligand treatment
  • More than 2 lines of prior taxane-based chemotherapy in castration-resistant setting
  • One or more extrahepatic soft tissue lesions negative on PSMA PET
  • Previous bilio-enteric anastomosis, biliary stent, or biliary drain through ampulla of Vater
  • Uncontrolled cardiovascular disease including NYHA Class 3-4 heart failure or myocardial infarction within 6 months
  • Active Hepatitis B or C infection unless treated with undetectable viral load
  • Not a candidate for liver-directed therapy due to bleeding diathesis or clinically significant ascites

NCT07140900

A Phase 1b Open-label, Multicenter Study Evaluating the Safety, Tolerability, and Efficacy of Xaluritamig in Combination With Androgen Receptor Pathway Inhibitors in Participants With Metastatic Hormone-sensitive Prostate Cancer

Organization/Sponsor: Amgen


Example patient: A 68-year-old man newly diagnosed with de novo metastatic hormone-sensitive prostate adenocarcinoma with liver metastases and 5 bone lesions including femur involvement, started on ADT 8 weeks ago with stable PSA.

Phase 1

Interventions

  • Drug: Abiraterone
    Summary: A CYP17 inhibitor that blocks 17α-hydroxylase/C17,20-lyase to reduce testosterone production in testes and adrenals, used with prednisone for metastatic castration-resistant and high-risk castration-sensitive prostate cancer (FDA label, NCI Thesaurus).
  • Drug: Darolutamide
    Summary: An androgen receptor inhibitor that blocks androgen receptors to prevent androgen-driven cancer cell growth, effective in nonmetastatic castration-resistant prostate cancer (Web Search Summary).
  • Biological: Xaluritamig
    Summary: A humanized IgG1 bispecific antibody targeting STEAP1 on tumor cells and CD3 on T-cells, cross-linking them to induce cytotoxic T-lymphocyte response against STEAP1-overexpressing prostate cancer cells (NCI Thesaurus).

Key Inclusion

  • Histologically confirmed adenocarcinoma of the prostate
  • De novo metastatic hormone-sensitive prostate cancer
  • Started ADT within 12 weeks before screening
  • High-volume metastatic disease with visceral metastasis or ≥4 bone metastases
  • At least one bone metastasis outside vertebral column and pelvis
  • Documented metastatic disease by bone scan or CT/MRI
  • PSA not progressing per PCWG3 after initial nadir
  • No prior docetaxel treatment

Key Exclusion

  • Prior CNS metastases
  • Prior STEAP1-targeted therapy
  • Prior radioligand therapy, PARP inhibitor, or chemotherapy for prostate cancer
  • Prior enzalutamide or apalutamide within 15 days
  • Chronic corticosteroid therapy >10 mg prednisone daily
  • Autoimmune disease requiring systemic immunosuppression within 2 years
  • Active or uncontrolled infection within 7 days
  • Prior radiotherapy to prostate or metastatic lesions except palliative radiation >2 weeks prior

NCT07216248

A Phase II Randomized, Decentralized, De-escalation Study in Patients With Metastatic Hormone-Sensitive Prostate Cancer Achieving Optimal PSA Response (OPTIMAS)

Organization/Sponsor: University of Utah


Example patient: A 62-year-old man with metastatic hormone-sensitive prostate adenocarcinoma who achieved PSA of 0.1 ng/mL after 8 months of relugolix and abiraterone, has ECOG status 1, owns a smartphone, and has no brain metastases or prior surgical castration.

Phase II

Interventions

  • DRUG: relugolix + ARPI
    Summary: Relugolix (ORGOVYX) is a nonpeptide GnRH receptor antagonist that blocks GnRH receptors to suppress testosterone production, slowing prostate cancer growth, combined with androgen receptor pathway inhibitors (ARPI) for advanced prostate cancer treatment (FDA label, NCI Thesaurus).
  • DRUG: relugolix or androgen deprivation therapy (ADT) + ARPI
    Summary: Combination of relugolix or other ADT (gonadotropin-releasing hormone agonists/antagonists) with ARPI to reduce serum male sex hormones for prostate cancer treatment (FDA label, NCI Thesaurus).
  • DRUG: Intermittent- Relugolix or androgen deprivation therapy (ADT) + ARPI
    Summary: Intermittent dosing regimen of relugolix or ADT combined with ARPI to reduce testosterone levels for advanced prostate cancer, allowing treatment breaks (FDA label, NCI Thesaurus).

Key Inclusion

  • Age ≥18 years
  • Metastatic hormone-sensitive prostate cancer with adenocarcinoma histology
  • Metastasis detected on conventional or functional imaging
  • PSA ≤0.2 ng/mL after 6-12 months of treatment (Cohort A Step 2) or after any duration (Cohort B)
  • ECOG Performance Status ≤2 (Cohort A)
  • Baseline testosterone >50 ng/dL before metastatic treatment (Cohort A)
  • Access to smartphone and wireless services
  • Eligible for relugolix and ARPI per investigator

Key Exclusion

  • Prior androgen deprivation therapy for metastatic disease (Cohort A Step 1)
  • History of surgical castration (Cohort B)
  • Progression to metastatic castration-resistant prostate cancer
  • Known untreated brain metastases or cranial epidural disease
  • Receiving other systemic anti-cancer therapy (Step 2 and Cohort B)
  • Another malignancy likely to impact safety or participation
  • Known severe hypersensitivity to study drug (Grade ≥3)
  • Taking prohibited medications

NCT06616155

Study of JAK Inhibition in Stem-Like Prostate Cancer (JASPER): A Phase 1b/2a Multicenter Study of Ruxolitinib and Enzalutamide in Castration Resistant Prostate Cancer

Organization/Sponsor: University of Michigan Rogel Cancer Center


Example patient: A 67-year-old man with metastatic castration-resistant prostate cancer who progressed after 5 months on abiraterone with rising PSA to 8.2 ng/mL, testosterone 25 ng/dL, ECOG 1, and adequate organ function.

Phase 1b, Phase 2a

Interventions

  • Drug: Ruxolitinib
    Summary: Ruxolitinib is an orally bioavailable JAK1/JAK2 inhibitor that blocks JAK-STAT signaling pathways involved in cellular proliferation, inflammation, and immune response. FDA-approved for myelofibrosis, polycythemia vera, and graft-versus-host disease; investigated here for antineoplastic activity in prostate cancer. Source: FDA label, NCI Thesaurus.
  • Drug: Enzalutamide
    Summary: Enzalutamide is an androgen receptor antagonist that blocks testosterone from fueling prostate cancer growth. FDA-approved for castration-resistant and non-metastatic castration-sensitive prostate cancer. Source: Web Search Summary.
  • Procedure: Computed Tomography
    Summary: Imaging modality using X-rays and computer reconstruction to create cross-sectional scans for monitoring disease progression and response. Source: NCI Thesaurus.
  • Procedure: Bone Scan
    Summary: Nuclear imaging method using radioactive tracer to detect bone metastases and evaluate pathological bone metabolism in prostate cancer. Source: NCI Thesaurus, Web Search Summary.
  • Procedure: Biospecimen Collection
    Summary: Collection of tissue or fluid samples for research, testing, and genetic analysis to study disease patterns and treatment response. Source: NCI Thesaurus, Web Search Summary.
  • Procedure: Biopsy
    Summary: Removal of metastatic tumor tissue for microscopic examination and molecular analysis to establish diagnosis and guide treatment. Source: NCI Thesaurus, Web Search Summary.

Key Inclusion

  • Males age ≥18 with progressive metastatic castration-resistant prostate cancer
  • Serum testosterone <50 ng/dL with continuous castration ≥8 weeks
  • Progressed on prior abiraterone by PCWG3 PSA criteria
  • Poor responder to abiraterone: <12 months in HSPC or <6 months in CRPC
  • Current or most recent treatment is ADT and abiraterone
  • PSA >2.0 ng/mL with two rising measurements ≥1 week apart
  • ECOG performance status 0-2
  • Adequate organ function: platelets ≥125,000/mm³, ANC ≥1500/mm³, hemoglobin ≥11 g/dL, CrCl ≥30 mL/min

Key Exclusion

  • Untreated brain metastasis
  • History of seizures or hypersensitivity to enzalutamide or ruxolitinib
  • Chemotherapy in metastatic CRPC setting
  • Active hepatitis B, hepatitis C, or tuberculosis
  • Myocardial infarction, stroke, or thromboembolism within 6 months
  • Uncontrolled hypertension: SBP >170 or DBP >105 mmHg
  • Underlying hepatic disease with Child-Pugh class A, B, or C impairment
  • Currently taking fluconazole or strong CYP2C8/CYP3A4 inhibitors or inducers

NCT07181161

A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0516 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Metastatic Prostate Cancer

Organization/Sponsor: AstraZeneca


Example patient: A 68-year-old man with metastatic castration-resistant prostate adenocarcinoma, PSA 15 ng/mL, testosterone 25 ng/dL on ongoing ADT, ECOG 1, with bone and soft tissue metastases showing radiographic progression, no prior chemotherapy or STEAP2-targeted therapy.

Phase I, Phase IIa

Interventions

  • Antibody-Drug Conjugate: AZD0516
    Summary: AZD0516 is an antibody-drug conjugate targeting STEAP2 that delivers cytotoxic therapy specifically to prostate cancer cells, currently evaluated for castration-resistant prostate cancer (Summary of Web Search).
  • PARP Inhibitor: AZD9574
    Summary: AZD9574 (palacaparib) is an orally bioavailable, CNS-penetrant PARP1 inhibitor that prevents DNA repair via base excision repair, promoting genomic instability and apoptosis in cancer cells (NCI Thesaurus).

Key Inclusion

  • Histologically or cytologically confirmed metastatic adenocarcinoma of the prostate
  • Measurable PSA ≥ 1 ng/mL
  • Castrated with serum testosterone ≤ 50 ng/dL
  • ECOG performance status 0 or 1
  • Documented mCRPC progression with PSA progression, soft tissue progression per RECIST v1.1, or bone progression
  • Life expectancy at least 12 weeks
  • Adequate organ and marrow function
  • Provision of baseline FFPE tumor sample mandatory

Key Exclusion

  • Symptomatic brain metastases or spinal cord compression requiring corticosteroids > 10 mg prednisone/day
  • History of leptomeningeal carcinomatosis
  • Unresolved toxicities Grade ≥ 2 from prior therapy
  • Cardiovascular disorders including uncontrolled hypertension, symptomatic heart failure, or cardiomyopathy
  • History of non-infectious interstitial lung disease or pneumonitis
  • Active infections including tuberculosis, HBV, HCV, or HIV
  • Myelodysplastic syndrome or acute myeloid leukemia
  • Previous treatment with STEAP2 targeting modality or topoisomerase inhibitor chemotherapy