Prostate Cancer MetastaticPhase 1/2NCT05067140
A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer
A Phase 1/2 study testing ARV-766, Abiraterone and Corticosteroid (e.g., prednisone/prednisolone) in people with Prostate Cancer Metastatic, run by Novartis Pharmaceuticals at 17 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer Metastatic
- What is being tested?
- ARV-766, Abiraterone and Corticosteroid (e.g., prednisone/prednisolone)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 17 sitesUnited States
- Study dates
- 2 Sep 2021to 25 May 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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
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- 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
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of >2.5× ULN if there is NO liver involvement secondary to tumor OR >5.0× ULN if there is liver involvement secondary to tumor
- Prior treatment with a second-generation NHA such as abiraterone, enzalutamide, darolutamide, or apalutamide (Part C only). Note: prior chemotherapy is allowed.
- Other inclusion/exclusion criteria may apply.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Chesapeake Urology Associates
Baltimore, Maryland, 21204
Massachusetts General Hospital
Boston, Massachusetts, 02114
Roswell Park Cancer Institute
Buffalo, New York, 14203
University of Virginia Medical Center
Charlottesville, Virginia, 22908
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope National Medical
Duarte, California, 91010
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Florida Cancer Specialists
Fort Myers, Florida, 33901
University of California San Diego - Moores Cancer Center
La Jolla, California, 92093-0658
University of Wisconsin Paul P Carbone Comp Cancer Center
Madison, Wisconsin, 53792-6164
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
SCRI Oncology Partners
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06520
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Univ of Pittsburgh Cancer Inst
Pittsburgh, Pennsylvania, 15232
Urology San Antonio
San Antonio, Texas, 78229
Providence Saint Johns Health Ctr
Santa Monica, California, 90404
About this study
Official title: A Phase 1/2 Open-Label, Dose-Escalation and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-766 Monotherapy and in Combination With Abiraterone in Patients With Metastatic Prostate Cancer
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.
Read the detailed description
The study consists of multiple parts.
- Part A evaluates JSB462 monotherapy in a dose-escalation setting to determine safety, tolerability, dose-limiting toxicities, and the maximum tolerated dose or recommended Phase 2 dose (RP2D). Dose escalation follows an accelerated titration design transitioning to a 3+3 design.
- Part B is a randomized cohort expansion evaluating JSB462 monotherapy at selected dose levels (e.g., 100 mg or 300 mg once daily) to further assess safety and preliminary antitumor activity at the RP2D. Participants are randomized in a 1:1 ratio.
- Part C evaluates JSB462 in combination with abiraterone, administered with corticosteroid and ongoing androgen deprivation therapy. This part assesses safety, tolerability, pharmacokinetics, and defines a recommended dose for the combination regimen. An abiraterone lead-in period is implemented prior to combination treatment.
The study population includes adult males with metastatic prostate cancer. In Parts A and B, participants have metastatic castration-resistant prostate cancer (mCRPC) following prior systemic therapy. Part C includes participants with metastatic prostate cancer, including those who may be naïve to novel hormonal agents.
Primary objectives focus on safety and tolerability, including incidence of adverse events, laboratory abnormalities, and dose-limiting toxicities. In the expansion phase, antitumor activity is evaluated using prostate-specific antigen (PSA) response rates (e.g., PSA30 and PSA50).
Secondary objectives include characterization of pharmacokinetics and further assessment of antitumor activity using endpoints such as objective response rate, radiographic progression-free survival, duration of response, and time to PSA progression. Tumor assessments are performed using modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for soft tissue disease and Prostate Cancer Working Group 3 (PCWG3) criteria for bone disease, with imaging conducted at regular intervals.
This study aims to characterize the clinical profile of JSB462 and explore its potential to overcome resistance mechanisms associated with androgen receptor signaling in metastatic prostate cancer.
- Conditions
- Prostate Cancer Metastatic
- Being tested
- ARV-766, Abiraterone, Corticosteroid (e.g., prednisone/prednisolone), Androgen Deprivation Therapy (ADT)
- 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
- Medical subject headings
- Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARV-766Drug
Also called JSB462; luxdegalutamide
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.
AbirateroneDrug
Also called Abiraterone acetate
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.
Corticosteroid (e.g., prednisone/prednisolone)Drug
Also called Prednisone; Prednisolone
Prednisone or prednisolone was administered in accordance with local prescribing information during treatment with abiraterone acetate.
Androgen Deprivation Therapy (ADT)Other
Also called LHRH agonist; LHRH antagonist
Ongoing androgen deprivation therapy, including luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or prior orchiectomy, is maintained per investigator choice or patient preference.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: ARV-766; Drug: Abiraterone; Drug: Corticosteroid (e.g., prednisone/prednisolone); Other: Androgen Deprivation Therapy (ADT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 12 Weeks
Secondary outcomes (22)
Part A: 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
Measured: 12 Weeks
Part A: 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
Measured: 12 Weeks
Part A: Objective Response Rate (ORR)
Overall Response Rate (ORR) is defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: 12 Weeks
Parts A and B: Radiographic Progression-Free Survival (rPFS)
Time from first dose to radiographic disease progression per modified RECIST Version 1.1 for soft tissue lesions and PCWG3 criteria for bone lesions, or death from any cause.
Measured: Baseline to radiographic progression or death, whichever occurs first, assessed up to 68 months
Parts A and B: Duration of Response (DoR)
Duration of Response (DOR) is defined as the time between first documented CR/PR and disease progression or death due to any cause per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: From first documented response to disease progression or death, whichever occurs first, assessed up to 68 months
Parts A and B: Time to Prostate-Specific Antigen Progression
Time to PSA progression is the time interval from the date of first study drug dose to the date of PSA progression. The PSA progression date is defined as the date that a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir is documented, which is confirmed by a second consecutive value obtained 3 or more weeks later
Measured: Baseline to prostate-specific antigen progression, assessed up to 68 months
Part A: Area Under the plasma Concentration-Time Curve (AUC) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUClast), Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) and Area under the plasma concentration-time curve from time zero during a dosing interval (AUCtau) will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Maximum Observed Concentration (Cmax) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Cmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Time to Maximum Concentration (Tmax) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Tmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Last Measurable Concentration (Clast) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Clast will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Minimum Observed Concentration (Cmin) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Cmin will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Apparent total body clearance (CL/F) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. CL/F will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Apparent Volume of Distribution (Vd/F) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Vd/F will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part B: 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.
Measured: From first dose through approximately 30 days after last dose
Part B: Incidence of laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing.
Measured: From first dose through approximately 30 days after last dose
Part C: Area Under the plasma Concentration-Time Curve (AUC) of Abiraterone/ARV-766
Venous whole blood samples will be collected for Abiraterone/ARV-766 characterization. Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUClast), Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) and Area under the plasma concentration-time curve from time zero during a dosing interval (AUCtau) will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Maximum Observed Concentration (Cmax) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Cmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Time to Maximum Concentration (Tmax) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Tmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Last Measurable Concentration (Clast) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Clast will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Minimum Observed Concentration (Cmin) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Cmin will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Apparent total body clearance (CL/F) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. CL/F will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Apparent Volume of Distribution (Vd/F) of ARV-766
Venous whole blood samples will be collected for ARV-766 characterization. Vd/F will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2021
- Study start2 Sep 2021
- Primary completion25 May 2027 (estimated)
- Study completion25 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05067140
- Sponsor's protocol ID
- CJSB462A12101
- Other IDs
- ARV-766-mCRPC-101
- Status last verified
- Jul 2026
- First submitted
- 23 Sep 2021
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-Label, Dose-Escalation and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-766 Monotherapy and in Combination With Abiraterone in Patients With Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT05067140
- Acronym / sponsor ID
- CJSB462A12101
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Sep 2021 (actual)
- Primary completion
- 25 May 2027 (estimated)
- Study completion
- 25 May 2027 (estimated)
- First posted
- 5 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study consists of multiple parts.
- Part A evaluates JSB462 monotherapy in a dose-escalation setting to determine safety, tolerability, dose-limiting toxicities, and the maximum tolerated dose or recommended Phase 2 dose (RP2D). Dose escalation follows an accelerated titration design transitioning to a 3+3 design.
- Part B is a randomized cohort expansion evaluating JSB462 monotherapy at selected dose levels (e.g., 100 mg or 300 mg once daily) to further assess safety and preliminary antitumor activity at the RP2D. Participants are randomized in a 1:1 ratio.
- Part C evaluates JSB462 in combination with abiraterone, administered with corticosteroid and ongoing androgen deprivation therapy. This part assesses safety, tolerability, pharmacokinetics, and defines a recommended dose for the combination regimen. An abiraterone lead-in period is implemented prior to combination treatment.
The study population includes adult males with metastatic prostate cancer. In Parts A and B, participants have metastatic castration-resistant prostate cancer (mCRPC) following prior systemic therapy. Part C includes participants with metastatic prostate cancer, including those who may be naïve to novel hormonal agents.
Primary objectives focus on safety and tolerability, including incidence of adverse events, laboratory abnormalities, and dose-limiting toxicities. In the expansion phase, antitumor activity is evaluated using prostate-specific antigen (PSA) response rates (e.g., PSA30 and PSA50).
Secondary objectives include characterization of pharmacokinetics and further assessment of antitumor activity using endpoints such as objective response rate, radiographic progression-free survival, duration of response, and time to PSA progression. Tumor assessments are performed using modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for soft tissue disease and Prostate Cancer Working Group 3 (PCWG3) criteria for bone disease, with imaging conducted at regular intervals.
This study aims to characterize the clinical profile of JSB462 and explore its potential to overcome resistance mechanisms associated with androgen receptor signaling in metastatic prostate cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A: ARV-766 Monotherapy (Dose Escalation) | Experimental | Drug: ARV-766, Other: Androgen Deprivation Therapy (ADT)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. |
| Part B: ARV-766 Monotherapy (Dose Expansion) | Experimental | Drug: ARV-766, Other: Androgen Deprivation Therapy (ADT)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. |
| Part C: ARV-766 + Abiraterone | Experimental | Drug: ARV-766, Drug: Abiraterone, Drug: Corticosteroid (e.g., prednisone/prednisolone), Other: Androgen Deprivation Therapy (ADT)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration) (Parts A and B only)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARV-766Also: JSB462; luxdegalutamideParts 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. | Drug | Part A: ARV-766 Monotherapy (Dose Escalation), Part B: ARV-766 Monotherapy (Dose Expansion), Part C: ARV-766 + Abiraterone |
| AbirateroneAlso: Abiraterone acetateAbiraterone is administered orally in combination with ARV-766, typically on an empty stomach with water, in accordance with prescribing information and standard clinical practice. | Drug | Part C: ARV-766 + Abiraterone |
| Corticosteroid (e.g., prednisone/prednisolone)Also: Prednisone; PrednisolonePrednisone or prednisolone was administered in accordance with local prescribing information during treatment with abiraterone acetate. | Drug | Part C: ARV-766 + Abiraterone |
| Androgen Deprivation Therapy (ADT)Also: LHRH agonist; LHRH antagonistOngoing androgen deprivation therapy, including luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or prior orchiectomy, is maintained per investigator choice or patient preference. | Other | Part A: ARV-766 Monotherapy (Dose Escalation), Part B: ARV-766 Monotherapy (Dose Expansion), Part C: ARV-766 + Abiraterone |
Primary outcome
Part A: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment
Time frame: Up to 28 days
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)
Part C: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment
Time frame: Up to 28 Days
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
Parts A and C: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose through approximately 30 days after last dose
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug.
Parts A and C: Incidence of laboratory abnormalities
Time frame: From first dose through approximately 30 days after last dose
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing.
Part B: Prostate-Specific Antigen 30% Response Rate (PSA30)
Time frame: 12 Weeks
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
Part B: Prostate-Specific Antigen 50% Response Rate (PSA50)
Time frame: 12 Weeks
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
22 secondary outcomes
Part A: Prostate-Specific Antigen 30% Response Rate (PSA30)
Time frame: 12 Weeks
Part A: Prostate-Specific Antigen 50% Response Rate (PSA50)
Time frame: 12 Weeks
Part A: Objective Response Rate (ORR)
Time frame: 12 Weeks
Parts A and B: Radiographic Progression-Free Survival (rPFS)
Time frame: Baseline to radiographic progression or death, whichever occurs first, assessed up to 68 months
Parts A and B: Duration of Response (DoR)
Time frame: From first documented response to disease progression or death, whichever occurs first, assessed up to 68 months
Parts A and B: Time to Prostate-Specific Antigen Progression
Time frame: Baseline to prostate-specific antigen progression, assessed up to 68 months
Part A: Area Under the plasma Concentration-Time Curve (AUC) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Maximum Observed Concentration (Cmax) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Time to Maximum Concentration (Tmax) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Last Measurable Concentration (Clast) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Minimum Observed Concentration (Cmin) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Apparent total body clearance (CL/F) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part A: Apparent Volume of Distribution (Vd/F) of ARV-766
Time frame: Cycle 1: Days 1 & 21 (0, 1, 2, 3, 4, 6, 8 and 12 hours), Day 2 (0 hour). Cycle 2 and beyond (0 hour). End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part B: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose through approximately 30 days after last dose
Part B: Incidence of laboratory abnormalities
Time frame: From first dose through approximately 30 days after last dose
Part C: Area Under the plasma Concentration-Time Curve (AUC) of Abiraterone/ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Maximum Observed Concentration (Cmax) of ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Time to Maximum Concentration (Tmax) of ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Last Measurable Concentration (Clast) of ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Minimum Observed Concentration (Cmin) of ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Apparent total body clearance (CL/F) of ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Part C: Apparent Volume of Distribution (Vd/F) of ARV-766
Time frame: Cycle 1 Days -8, -1, 1, 21, and 28; Cycle 2 Day 28; and Cycle ≥3 Day 28 (odd cycles only), with intensive post-dose PK on Days -1, 1, and 21; End of Treatment Visit (EOT): within 4 weeks from the last dose of ARV-766. 1 cycle = 28 days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ARV-766, Abiraterone and Corticosteroid (e.g., prednisone/prednisolone) in people with Prostate Cancer Metastatic, run by Novartis Pharmaceuticals at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment (time frame: Up to 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.