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
- 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.
- Short title
- 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
- 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
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2030-06-03
- First posted
- 2026-05-06
- Registry last updated
- 2026-07-14
- Primary completion date
- 2030-06-03
- Start date
- 2026-05-25
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Novartis Pharmaceuticals
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT07570979
- ClinicalTrials.gov ID
- NCT07570979
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Incidence and severity of dose-limiting toxicities (DLTs)
Timeframe: 28 days
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.
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timeframe: Up to approximately 24 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and electrocardiograms (ECGs) qualifying and reported as AEs.
Frequency of dose interruptions and reductions
Timeframe: Up to approximately 24 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
Dose intensity
Timeframe: Up to approximately 24 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
Overall Response Rate (ORR)
Timeframe: Up to approximately 24 months
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.
Disease Control Rate (DCR)
Timeframe: Up to approximately 24 months
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.
Radiological Progression Free Survival (rPFS)
Timeframe: Up to approximately 24 months
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.
Prostate-Specific Antigen 50% response rate (PSA50 rate)
Timeframe: Up to approximately 24 months
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.
Area under the plasma concentration-time curve (AUC) of INR731
Timeframe: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Pharmacokinetic (PK) parameters based on plasma concentrations of INR731.
Maximum plasma concentration (Cmax) of INR731
Timeframe: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
PK parameters based on plasma concentrations of INR731.
Time to reach maximum plasma concentration (Tmax) of INR731
Timeframe: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
PK parameters based on plasma concentrations of INR731.
Trough concentration (Ctrough) of INR731
Timeframe: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
PK parameters based on plasma concentrations of INR731.
Plasma concentrations of study drugs
Timeframe: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Concentration versus time profiles of study drugs.
Progression Free Survival (PFS)
Timeframe: Up to approximately 24 months
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.
- Sex
- Male
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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.
- 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.
- Mary Crowley Cancer ResearchDallas, United StatesRecruiting
- Novartis Investigative SiteMelbourne, AustraliaRecruiting
- Novartis Investigative SiteHirakata, JapanRecruiting
- 2025
- 2025-524080-20
Related records
Drugs (2)
Lead sponsors (1)
Conditions (2)
- Peritoneum cancer Primary condition
- Prostate cancer