Metastatic Castration-resistant Prostate Cancer (mCRPC)Phase 1NCT07570979
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
A Phase 1 study testing INR731, Enzalutamide and Abiraterone in people with Metastatic Castration-resistant Prostate Cancer (mCRPC), run by Novartis Pharmaceuticals at 13 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer (mCRPC)
- What is being tested?
- INR731, Enzalutamide and Abiraterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 13 sitesin 8 countries
- Study dates
- 25 May 2026to 3 Jun 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
13 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
13 sites in 8 countries
United States2 sites, 2 recruiting
- Recruiting
Mass General Hospital
Boston, Massachusetts, 02114
Nadia Kelley, nkelley4@mgh.harvard.edu
Xin Gao
- Recruiting
Mary Crowley Cancer Research
Dallas, Texas, 75251
Pramitha Kondancheri, +1 972 566 3000, Pramitha.RarothKondancheri@scri.com
Reva Schneider
Canada2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Montreal, Quebec, H2X 1R9
- Recruiting
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Germany2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Dresden, Saxony, 01307
- Recruiting
Novartis Investigative Site
Würzburg, Bavaria, 97080
South Korea2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Seoul, 03722
- Recruiting
Novartis Investigative Site
Seoul, 05505
Spain2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Madrid, 28034
- Recruiting
Novartis Investigative Site
Valencia, 46010
Australia1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Melbourne, Victoria, 3000
Italy1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Milan, MI, 20162
Japan1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Hirakata, Osaka, 5731191
About this study
Official title: 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.
Read the 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.
- Being tested
- INR731, Enzalutamide, Abiraterone, Androgen deprivation therapy (ADT)
- Keywords
- INR731, prostate cancer, mCRPC, castration resistance, androgen receptor pathway inhibitor, ARPI, abiraterone, enzalutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INR731Drug
Oral administration
EnzalutamideDrug
Oral administration
AbirateroneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| INR731 single agent (Arm A) | Experimental | The dose escalation part with single agent INR731 may be followed by a dose expansion part. Receives: 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. Receives: 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. Receives: Drug: INR731; Drug: Abiraterone; Drug: Androgen deprivation therapy (ADT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to approximately 24 months
Frequency of dose interruptions and reductions
Number of participants with dose interruptions and/or reductions to assess the tolerability.
Measured: Up to approximately 24 months
Dose intensity
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
Measured: Up to approximately 24 months
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 24 months
Area under the plasma concentration-time curve (AUC) of INR731
Pharmacokinetic (PK) parameters based on plasma concentrations of INR731.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2026
- Study start25 May 2026
- Primary completion3 Jun 2030 (estimated)
- Study completion3 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-resistant Prostate Cancer (mCRPC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 208 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07570979
- Sponsor's protocol ID
- CINR731A12101
- Other IDs
- 2025-524080-20, 2025
- Status last verified
- Oct 2026
- First submitted
- 30 Apr 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.