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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-524080-20 | Registry Identifier | EU registry (CTIS) |
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The purpose of this study is to assess the safety, tolerability, pharmacokinetics/pharmacodynamics, preliminary anti-tumor activity, and recommended dose of INR731 as a single agent and in combination with standard-of-care androgen receptor pathway inhibitors (ARPIs) in adult patients with metastatic prostate cancer.
This is a first-in-human, open-label, phase I, multi-center study which consists of three treatment arms: INR731 single agent (Arm A), and INR731 in combination with enzalutamide (Arm B) or abiraterone (Arm C).
The single agent arm has a dose escalation part followed by a dose expansion part. Once the single agent recommended dose(s) is determined during dose escalation, the study may proceed to dose expansion to further explore safety, tolerability and preliminary anti-tumor activity. The single agent dose expansion part will include a post-standard of care (SOC) metastatic castration resistant prostate cancer (mCRPC) group and patients with time to castration resistance (TTCR) <12 months.
The combination arms have a dose escalation of INR731 in combination with enzalutamide or abiraterone followed by a dose expansion of INR731 in combination with enzalutamide only. The combination dose escalation will be conducted in patients with mCRPC who have progressed following standard of care (post-SOC). During combination escalation, once the safety and tolerability of INR731 with the combination agent(s) is assessed, the study may proceed to dose expansion. The combination dose expansion part will include first-line (1L) mCRPC patients with no prior treatment in the mCRPC setting.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| INR731 single agent (Arm A) | Experimental | The dose escalation part with single agent INR731 may be followed by a dose expansion part. |
|
| INR731 in combination with enzalutamide (Arm B) | Experimental | The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part. |
|
| INR731 in combination with abiraterone (Arm C) | Experimental | Dose escalation of INR731 in combination with abiraterone. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INR731 | Drug | Oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and severity of dose-limiting toxicities (DLTs) | A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 that occurs within the first 28 days and not clearly and incontrovertibly assessed as due to disease progression, intercurrent illness, concomitant medication, or extraneous causes with the exceptions defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher. | 28 days |
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and electrocardiograms (ECGs) qualifying and reported as AEs. | Up to approximately 24 months |
| Frequency of dose interruptions and reductions | Number of participants with dose interruptions and/or reductions to assess the tolerability. | Up to approximately 24 months |
| Dose intensity | Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure. | Up to approximately 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | ORR is defined as proportion of patients achieving a confirmed complete response (CR) or partial response (PR) per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by the investigator. | Up to approximately 24 months |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Novartis Pharmaceuticals | Contact | 1-888-669-6682 | novartis.email@novartis.com | |
| Novartis Pharmaceuticals | Contact | +41613241111 |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mary Crowley Cancer Research | Recruiting | Dallas | Texas | 75251 | United States |
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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| Enzalutamide | Drug | Oral administration |
|
| Abiraterone | Drug | Oral administration |
|
| Androgen deprivation therapy (ADT) | Drug | Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care. |
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| Disease Control Rate (DCR) |
DCR is defined as proportion of patients achieving a CR, PR or stable disease (SD) per PCWG3-modified RECIST v1.1 as assessed by the investigator. |
| Up to approximately 24 months |
| Radiological Progression Free Survival (rPFS) | rPFS is defined as the time from the date of start of treatment to the date of the first documented radiological progression according to PCWG3-modified RECIST v1.1 or death due to any cause. | Up to approximately 24 months |
| Prostate-Specific Antigen 50% response rate (PSA50 rate) | PSA50 rate is defined as the proportion of patients who achieve a ≥50% decrease in prostate-specific antigen (PSA) from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks later without any PSA progression in between. | Up to approximately 24 months |
| Area under the plasma concentration-time curve (AUC) of INR731 | Pharmacokinetic (PK) parameters based on plasma concentrations of INR731. | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days. |
| Maximum plasma concentration (Cmax) of INR731 | PK parameters based on plasma concentrations of INR731. | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days. |
| Time to reach maximum plasma concentration (Tmax) of INR731 | PK parameters based on plasma concentrations of INR731. | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days. |
| Trough concentration (Ctrough) of INR731 | PK parameters based on plasma concentrations of INR731. | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days. |
| Plasma concentrations of study drugs | Concentration versus time profiles of study drugs. | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days. |
| Progression Free Survival (PFS) | PFS is defined as time from date of start of treatment to the first documented progression (radiological, clinical, or PSA progression) or death from any cause, whichever occurs first. | Up to approximately 24 months |
| Novartis Investigative Site | Recruiting | Melbourne | Victoria | 3000 | Australia |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C540278 | enzalutamide |
| C089740 | abiraterone |
| D000726 | Androgen Antagonists |
| ID | Term |
|---|---|
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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