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

NCT07570979 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CINR731A121012025-524080-20
• Study Type: interventional
• Target: 208
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Castration-resistant Prostate Cancer (mCRPC)

Keywords

INR731; prostate cancer; mCRPC; castration resistance; androgen receptor pathway inhibitor; ARPI; abiraterone; enzalutamide

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (10)

• Overall Response Rate (ORR)

  Up to approximately 24 months

• Disease Control Rate (DCR)

  Up to approximately 24 months

• Radiological Progression Free Survival (rPFS)

  Up to approximately 24 months

• Prostate-Specific Antigen 50% response rate (PSA50 rate)

  Up to approximately 24 months

• Area under the plasma concentration-time curve (AUC) of INR731

  From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.

Study Arms (3)

INR731 single agent (Arm A)

EXPERIMENTAL

The dose escalation part with single agent INR731 may be followed by a dose expansion part.

Drug: INR731; Drug: Androgen deprivation therapy (ADT)

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.

Drug: INR731; Drug: Enzalutamide; Drug: Androgen deprivation therapy (ADT)

INR731 in combination with abiraterone (Arm C)

EXPERIMENTAL

Dose escalation of INR731 in combination with abiraterone.

Drug: INR731; Drug: Abiraterone; Drug: Androgen deprivation therapy (ADT)

Interventions

INR731 DRUG

Oral administration

INR731 in combination with abiraterone (Arm C); INR731 in combination with enzalutamide (Arm B); INR731 single agent (Arm A)

Enzalutamide DRUG

Oral administration

INR731 in combination with enzalutamide (Arm B)

Abiraterone DRUG

Oral administration

INR731 in combination with abiraterone (Arm C)

Androgen deprivation therapy (ADT) DRUG

Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.

INR731 in combination with abiraterone (Arm C); INR731 in combination with enzalutamide (Arm B); INR731 single agent (Arm A)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; abiraterone; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2026
• First Posted: May 6, 2026
• Study Start (Estimated): May 26, 2026
• Primary Completion (Estimated): June 3, 2030
• Study Completion (Estimated): June 3, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); AU (1)