Active, not recruiting
Phase 1/2
A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer
Condition(s) studied
Prostate Cancer Metastatic
Investigational drug(s) / intervention(s)
ARV-766AbirateroneCorticosteroid (e.g., prednisone/prednisolone)Androgen Deprivation Therapy (ADT)
ARV-766: 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.
Abiraterone: 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): Prednisone or prednisolone was administered in accordance with local prescribing information during treatment with abiraterone acetate.
Androgen Deprivation Therapy (ADT): Ongoing androgen deprivation therapy, including luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or prior orchiectomy, is maintained per investigator choice or patient preference.
Study 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.
Eligibility
Key Inclusion Criteria for Parts A, B, and C:
* 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)
Key Exclusion Criteria for Parts A, B, and C:
* 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
* 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.
Primary outcome measure(s)
- Part A: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment — 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 — 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) — 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 — 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) — 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) — 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
Trial sites (17)
| Facility | City | Region | Status |
| City of Hope National Medical |
Duarte |
California |
|
| University of California San Diego - Moores Cancer Center |
La Jolla |
California |
|
| Providence Saint Johns Health Ctr |
Santa Monica |
California |
|
| Yale Cancer Center |
New Haven |
Connecticut |
|
| Florida Cancer Specialists |
Fort Myers |
Florida |
|
| Chesapeake Urology Associates |
Baltimore |
Maryland |
|
| Massachusetts General Hospital |
Boston |
Massachusetts |
|
| Karmanos Cancer Institute |
Detroit |
Michigan |
|
| Roswell Park Cancer Institute |
Buffalo |
New York |
|
| Fox Chase Cancer Center |
Philadelphia |
Pennsylvania |
|
| Univ of Pittsburgh Cancer Inst |
Pittsburgh |
Pennsylvania |
|
| Carolina Urologic Research Center |
Myrtle Beach |
South Carolina |
|
| SCRI Oncology Partners |
Nashville |
Tennessee |
|
| Urology San Antonio |
San Antonio |
Texas |
|
| University of Virginia Medical Center |
Charlottesville |
Virginia |
|
| Virginia Cancer Specialists |
Fairfax |
Virginia |
|
| University of Wisconsin Paul P Carbone Comp Cancer Center |
Madison |
Wisconsin |
|
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