A Study to Investigate the Safety and Tolerability of Oral INR731 Single Agent or in Combination With Androgen Receptor Pathway Inhibitor (ARPI) in Patients With Metastatic Prostate Cancer

An Open-label, Multi-center, First in Human Phase I Global Dose Escalation and Expansion Study of INR731 Single Agent or in Combination With an Androgen Receptor Pathway Inhibitor in Patients With Metastatic Prostate Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Intervention / Treatment: Drug: INR731; Drug: Androgen deprivation therapy (ADT); Drug: Enzalutamide; Drug: Abiraterone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Novartis Investigative Site
• United States
  • Texas
    • Dallas, Texas, United States, 75251
      • Recruiting
      • Mary Crowley Cancer Research
      • Principal Investigator: Reva Schneider
      • Contact: Pramitha Kondancheri; Phone Number: 972-566-3000; Email: Pramitha.RarothKondancheri@scri.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2.
• Participants must have histological and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are eligible as long as the non-adenocarcinoma feature is the minority component.
• At least 1 metastatic lesion (according to local radiology assessment by the investigator) present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to Cycle 1 Day 1 (C1D1).
• Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
• Ongoing androgen deprivation therapy (ADT) either via orchiectomy and/or ongoing gonadotropin-releasing hormone (GnRH) analog or inhibitor is allowed.
• Participants must be mCRPC patients who have either progressed on or are not candidates for other SOC. Prior taxane, poly(ADP) ribose polymerase (PARP) inhibitor, and lutetium Lu 177 vipivotide tetraxetan (Pluvicto) are allowed. Combination expansion patients, however, must be 1L mCRPC with no prior treatment in the mCRPC setting. Treatment within the mHSPC setting does not affect eligibility.

Exclusion Criteria:

• Age < 18 years old.
• Histological and/or cytological confirmation of non-adenocarcinoma of the prostate.
• Patients with biochemical recurrence only or those without evidence of metastatic disease by radiographical imaging (CT/MRI or bone scan) are not eligible.
• Patients previously treated with a cereblon-based degrader.
• Patients who are HIV+ or immune compromised.
• Use of agents known to prolong QT interval unless they can be permanently discontinued for the duration of the study
• Treatment with an investigational agent within 7 days (or 5 half-lives, whichever is longer) of the anticipated Cycle 1 Day 1 (C1D1).

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INR731 single agent (Arm A); The dose escalation part with single agent INR731 may be followed by a dose expansion part.	Drug: INR731; Oral administration; Drug: Androgen deprivation therapy (ADT); Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Experimental: INR731 in combination with enzalutamide (Arm B); The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part.	Drug: INR731; Oral administration; Drug: Androgen deprivation therapy (ADT); Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.; Drug: Enzalutamide; Oral administration
Experimental: INR731 in combination with abiraterone (Arm C); Dose escalation of INR731 in combination with abiraterone.	Drug: INR731; Oral administration; Drug: Androgen deprivation therapy (ADT); Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.; Drug: Abiraterone; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2026
• Primary Completion (Estimated): June 3, 2030
• Study Completion (Estimated): June 3, 2030

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: prostate cancer; enzalutamide; mCRPC; abiraterone; ARPI; INR731; castration resistance; androgen receptor pathway inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Androgen Antagonists; abiraterone; enzalutamide
• Other Study ID Numbers: CINR731A12101; 2025-524080-20 (Registry Identifier: EU registry (CTIS))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No