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

Novartis

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT07570979

2025-524080-20 (Registry Identifier)

CINR731A12101

2025

Details and patient eligibility

About

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.

Full 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.

Enrollment: 208 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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208 participants in 3 patient groups

INR731 single agent (Arm A)

Experimental group

Description:

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

Treatment:

Drug: Androgen deprivation therapy (ADT)

Drug: INR731

INR731 in combination with enzalutamide (Arm B)

Experimental group

Description:

The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part.

Treatment:

Drug: Androgen deprivation therapy (ADT)

Drug: Enzalutamide

Drug: INR731

INR731 in combination with abiraterone (Arm C)

Experimental group

Description:

Dose escalation of INR731 in combination with abiraterone.

Treatment:

Drug: Androgen deprivation therapy (ADT)

Drug: INR731

Drug: Abiraterone