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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

10. september 2026 oppdatert av: Novartis Pharmaceuticals

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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

208

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

  • Navn: Novartis Pharmaceuticals
  • Telefonnummer: +41613241111

Studiesteder

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Rekruttering
        • Novartis Investigative Site
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H2X 1R9
        • Rekruttering
        • Novartis Investigative Site
  • Forente stater
    • Texas
      • Dallas, Texas, Forente stater, 75251
        • Rekruttering
        • Mary Crowley Cancer Research
        • Hovedetterforsker:
          • Reva Schneider
        • Ta kontakt med:
  • Japan
    • Osaka
      • Hirakata, Osaka, Japan, 5731191
        • Rekruttering
        • Novartis Investigative Site
  • Sør -Korea
      • Seoul, Sør -Korea, 03722
        • Rekruttering
        • Novartis Investigative Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: INR731 single agent (Arm A)
The dose escalation part with single agent INR731 may be followed by a dose expansion part.
Legemiddel: INR731
Oral administration
Legemiddel: Androgen deprivation therapy (ADT)
Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Eksperimentell: 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.
Legemiddel: INR731
Oral administration
Legemiddel: Androgen deprivation therapy (ADT)
Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Legemiddel: Enzalutamide
Oral administration
Eksperimentell: INR731 in combination with abiraterone (Arm C)
Dose escalation of INR731 in combination with abiraterone.
Legemiddel: INR731
Oral administration
Legemiddel: Androgen deprivation therapy (ADT)
Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Legemiddel: Abiraterone
Oral administration

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Incidence and severity of dose-limiting toxicities (DLTs)
Tidsramme: 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.
28 days
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: 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.
Up to approximately 24 months
Frequency of dose interruptions and reductions
Tidsramme: Up to approximately 24 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
Up to approximately 24 months
Dose intensity
Tidsramme: Up to approximately 24 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
Up to approximately 24 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall Response Rate (ORR)
Tidsramme: 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.
Up to approximately 24 months
Disease Control Rate (DCR)
Tidsramme: 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.
Up to approximately 24 months
Radiological Progression Free Survival (rPFS)
Tidsramme: 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.
Up to approximately 24 months
Prostate-Specific Antigen 50% response rate (PSA50 rate)
Tidsramme: 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.
Up to approximately 24 months
Area under the plasma concentration-time curve (AUC) of INR731
Tidsramme: 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.
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
Tidsramme: 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.
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
Tidsramme: 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.
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
Tidsramme: 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.
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
Tidsramme: 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.
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)
Tidsramme: 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.
Up to approximately 24 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Novartis Pharmaceuticals

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

25. mai 2026

Primær fullføring (Antatt)

3. juni 2030

Studiet fullført (Antatt)

3. juni 2030

Datoer for studieregistrering

Først innsendt

30. april 2026

Først innsendt som oppfylte QC-kriteriene

30. april 2026

Først lagt ut (Faktiske)

6. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

11. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

10. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CINR731A12101
  • 2025 (U.S. NIH-stipend/kontrakt: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • 2025-524080-20 (Registeridentifikator: EU registry (CTIS))

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

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.

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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