Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as JSB462, ARV-766, JSB462 Dose 1 QD, JSB462 Dose 1, JSB462 Dose 2 QD, JSB462 QD
Luxdegalutamide · 4 trials · 4 indications
Prostate Specific Antigen 90 (PSA90) Rate is defined as the proportion of participants who achieve a ≥90% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between.
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
The duration of exposure in weeks to study treatment and for each study treatment component (JSB462, abiraterone and enzalutamide) will be summarized for each study treatment component by means of descriptive statistics using the SAS.
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
A dose-limiting toxicity (DLT) is defined as a treatment-related adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the first 28 days of treatment with JSB462 and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose regimen decisions, DLTs will be considered.
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics.
JSB462 pharmacokinetic (PK) samples will be obtained and evaluated to assess single dose and steady-state plasma Pharmacokinetic (PK) of JSB462 and its metabolite ARV-767 and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) and Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
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)
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
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug.
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing.
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
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
| Arm | Type | Description |
|---|---|---|
| Arm 1 | EXPERIMENTAL | JSB462 100 mg QD + abiraterone 1000 mg QD |
| Arm 2 | EXPERIMENTAL | JSB462 300 mg QD + abiraterone 1000 mg QD |
| Arm 3 | ACTIVE_COMPARATOR | abiraterone 1000 mg QD or enzalutamide 160 mg QD |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| JSB462 | DRUG | JSB462 is administered orally, daily and continuously (100 mg or 300 mg QD) until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision. |
| Abiraterone | DRUG | Abiraterone 1000 mg is administered orally, daily and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision. |
| Enzalutamide | DRUG | Enzalutamide 160 mg is administered orally, daily and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision. |
| AAA617 | DRUG | administered at 7.4 GBq intravenously every 6 weeks for up to 6 doses, unless there is disease progression per PCWG3-modified RECIST v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision |
| 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. |
| Corticosteroid (e.g., prednisone/prednisolone) | DRUG | Prednisone or prednisolone was administered in accordance with local prescribing information during treatment with abiraterone acetate. |
| 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. |
Key Inclusion Criteria: * An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2 * Histologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible * High-volume mHSPC, defined by the presence of ≥1 metastatic visceral non...
Luxdegalutamide is an investigational oral small molecule being developed by Novartis AG for prostate cancer. It is in Phase 2 clinical development and is being studied in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer. It has not been approved by the FDA and remains under clinical investigation.
Luxdegalutamide is being studied for the treatment of prostate cancer, specifically metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer. Clinical trials are evaluating it both as a single agent and in combination with other therapies, including abiraterone and lutetium (177Lu) vipivotide tetraxetan.
Luxdegalutamide is developed by Novartis AG, which trades under the ticker NVS. Novartis is running the clinical development program, which includes Phase 1 and Phase 2 studies in Japan, the United States, and multiple other countries across Europe, Asia, and Australia.
Luxdegalutamide is in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. Two Phase 2 trials and two Phase 1 trials are registered, all currently active but not recruiting, with a combined enrollment of approximately 170 patients across the studies.
Luxdegalutamide is being evaluated in NCT07174063, a Phase 1 study in Japanese patients with metastatic prostate cancer; NCT07047118, a Phase 2 study combined with lutetium (177Lu) vipivotide tetraxetan in metastatic castration-resistant prostate cancer; and NCT06991556, a Phase 2 study combined with abiraterone in metastatic hormone-sensitive prostate cancer. A Phase 1 study, NCT05067140, evaluated ARV-766 in metastatic prostate cancer.
Yes. Luxdegalutamide is also known as ARV-766 and JSB462. ARV-766 was the earlier designation used in a Phase 1 study of the drug in men with metastatic prostate cancer, while JSB462 appears in the newer Novartis-sponsored trial titles, including the Japanese Phase 1 study and the Phase 2 combination studies.