A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer

NCT05067140 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CJSB462A12101ARV-766-mCRPC-101
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 17

Brief Summary

This first-in-human, Phase 1/2, open-label study evaluates the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of JSB462 (luxdegalutamide, previously ARV-766) administered as monotherapy and in combination with abiraterone in participants with metastatic prostate cancer. The study includes dose-escalation and cohort expansion components to determine the recommended Phase 2 dose and assess clinical activity.

Conditions

Prostate Cancer Metastatic

Keywords

Metastatic Prostate Cancer; Castrate-Resistant; Prostate Cancer; mCRPC adenocarcinoma of prostate; Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Castrate-Sensitive; mCSPC adenocarcinoma of prostate

Outcome Measures

Primary Outcomes (6)

• Part A: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment

  Number and proportion of participants experiencing dose-limiting toxicities during the DLT evaluation period to assess safety and determine the maximum tolerated dose (MTD) of ARV-766 and/or recommended Phase 2 dose (RP2D)

  Up to 28 days

• Part C: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment

  Number and proportion of participants experiencing dose-limiting toxicities during the DLT evaluation period to determine the recommended dose of ARV-766 in combination with abiraterone

  Up to 28 Days

• Parts A and C: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug.

  From first dose through approximately 30 days after last dose

• Parts A and C: Incidence of laboratory abnormalities

  Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing.

  From first dose through approximately 30 days after last dose

• Part B: Prostate-Specific Antigen 30% Response Rate (PSA30)

  Prostate Specific Antigen 30 (PSA30) Rate is defined as the proportion of participants who achieve a ≥30% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between

  12 Weeks

• Part B: Prostate-Specific Antigen 50% Response Rate (PSA50)

  Prostate Specific Antigen 50 (PSA50) Rate is defined as the proportion of participants who achieve a ≥50% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between

  12 Weeks

Secondary Outcomes (22)

• Part A: Prostate-Specific Antigen 30% Response Rate (PSA30)

  12 Weeks

• Part A: Prostate-Specific Antigen 50% Response Rate (PSA50)

  12 Weeks

• Part A: Objective Response Rate (ORR)

  12 Weeks

• Parts A and B: Radiographic Progression-Free Survival (rPFS)

  Baseline to radiographic progression or death, whichever occurs first, assessed up to 68 months

• Parts A and B: Duration of Response (DoR)

  From first documented response to disease progression or death, whichever occurs first, assessed up to 68 months

Study Arms (3)

Part A: ARV-766 Monotherapy (Dose Escalation)

EXPERIMENTAL

Participants with metastatic prostate cancer received escalating dose levels of ARV-766 administered orally to evaluate safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose and/or recommended Phase 2 dose. Participants continued androgen deprivation therapy as clinically indicated.

Drug: ARV-766; Other: Androgen Deprivation Therapy (ADT)

Part B: ARV-766 Monotherapy (Dose Expansion)

EXPERIMENTAL

Participants with metastatic castration-resistant prostate cancer received ARV-766 administered orally at selected dose levels to further evaluate antitumor activity, safety, tolerability, and pharmacokinetics. Participants continued androgen deprivation therapy as clinically indicated.

Drug: ARV-766; Other: Androgen Deprivation Therapy (ADT)

Part C: ARV-766 + Abiraterone

EXPERIMENTAL

Participants received ARV-766 in combination with abiraterone acetate and a corticosteroid (prednisone or prednisolone) to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the combination regimen. Participants continued androgen deprivation therapy as clinically indicated.

Drug: ARV-766; Drug: Abiraterone; Drug: Corticosteroid (e.g., prednisone/prednisolone); Other: Androgen Deprivation Therapy (ADT)

Interventions

ARV-766 DRUG

Parts A and C: Daily oral dosages are determined by cohort review committee after initial starting dose cohort and each subsequent cohort completes 28 days of treatment. Part B: 100mg or 300mg oral tablet(s) once daily in 28 day cycles.

Also known as: JSB462; luxdegalutamide

Part A: ARV-766 Monotherapy (Dose Escalation); Part B: ARV-766 Monotherapy (Dose Expansion); Part C: ARV-766 + Abiraterone

Abiraterone DRUG

Abiraterone is administered orally in combination with ARV-766, typically on an empty stomach with water, in accordance with prescribing information and standard clinical practice.

Also known as: Abiraterone acetate

Part C: ARV-766 + Abiraterone

Corticosteroid (e.g., prednisone/prednisolone) DRUG

Prednisone or prednisolone was administered in accordance with local prescribing information during treatment with abiraterone acetate.

Also known as: Prednisone; Prednisolone

Part C: ARV-766 + Abiraterone

Androgen Deprivation Therapy (ADT) OTHER

Ongoing androgen deprivation therapy, including luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or prior orchiectomy, is maintained per investigator choice or patient preference.

Also known as: LHRH agonist; LHRH antagonist

Part A: ARV-766 Monotherapy (Dose Escalation); Part B: ARV-766 Monotherapy (Dose Expansion); Part C: ARV-766 + Abiraterone

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be able to take oral medication without crushing, dissolving, or chewing tablets
• Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate
• Progression on approved systemic therapies for metastatic prostate cancer (at least one must be a second-generation androgen inhibitor, e.g., abiraterone, enzalutamide, darolutamide, apalutamide) (Parts A and B only)
• Progressive mCRPC (Parts A and B only) defined as:
• Serum testosterone levels \<50 ng/dL (or ≤0.50 ng/mL or 1.73 nmol/L) using testosterone assays with a sensitivity of ≤30 ng/dL, within 28 days before study drug treatment
• Radiographic evidence of metastatic disease (soft tissue disease per modified RECIST 1.1 criteria or bone disease per PCWG3)
• Disease progression on or following the most recent systemic therapy
• Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration) (Parts A and B only)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Metastatic castration resistant or sensitive prostate cancer with radiographic evidence of metastatic disease (soft tissue disease per modified RECIST 1.1 criteria or bone disease per PCWG3) (Part C)

You may not qualify if:

• Known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
• Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ or other low grade localized cancer. Eligibility for exception requires Sponsor approval
• Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolic disease
• Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock (bifascicular block). Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation). Anticoagulation (heparin/lovenox only) can be allowed if indicated
• QTcF \>480 msec at baseline based on ECG
• Active inflammatory gastrointestinal disease, chronic diarrhea, diverticulitis, or previous gastric resection or lap band surgery
• Participants taking sensitive BCRP and P-glycoprotein (P-gp) substrates or substrates with narrow therapeutic indices, strong CYP3A4 inhibitors and inducers, restricted medications described in the study protocol and the Investigator's Brochure, and additionally for Part C, CYP2D6 substrates with a narrow therapeutic index
• Inadequate bone marrow function defined as follows (with no transfusion of blood products or use of hematopoietic growth factors in the 28 days prior to start of therapy):
• Absolute neutrophil count \<1,500/mm3 or \<1.5 × 109/L
• Platelets \<100,000/mm3 or \<100 × 109/L
• Hemoglobin \<9 g/dL
• Inadequate renal function defined as estimated creatinine clearance (Clcr) ≤60 mL/min using Cockcroft-Gault formula or eGFR ≤60 mL/min/1.73m3 using the CKD-EPI equation
• Electrolyte imbalances of clinically significant hypokalemia, hypomagnesemia, and/or hypocalcemia (Part C only)
• Inadequate liver function defined as:
• Total serum bilirubin \>1.5× upper limit of normal (ULN) unless the participant has documented Gilbert syndrome

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

City of Hope National Medical

Duarte, California, 91010, United States

Location

University of California San Diego - Moores Cancer Center

La Jolla, California, 92093-0658, United States

Location

Providence Saint Johns Health Ctr

Santa Monica, California, 90404, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Chesapeake Urology Associates

Baltimore, Maryland, 21204, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Univ of Pittsburgh Cancer Inst

Pittsburgh, Pennsylvania, 15232, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Urology San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin Paul P Carbone Comp Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms

Interventions

abiraterone; Abiraterone Acetate; Adrenal Cortex Hormones; Prednisone; Prednisolone; Androgen Antagonists; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols; Pregnadienes; Pregnanes; Pregnadienetriols; Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 5, 2021
• Study Start: September 2, 2021
• Primary Completion (Estimated): May 25, 2027
• Study Completion (Estimated): May 25, 2027
• Last Updated: August 18, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (17)