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
2026年5月27日 更新者：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.
調査の概要
状態
募集
詳細な説明
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.
研究の種類
介入
入学 (推定)
208
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Novartis Pharmaceuticals
- 電話番号：1-888-669-6682
- メール：novartis.email@novartis.com
研究連絡先のバックアップ
- 名前：Novartis Pharmaceuticals
- 電話番号：+41613241111
研究場所
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Texas
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Dallas、Texas、アメリカ、75251
- 募集
- Mary Crowley Cancer Research
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主任研究者：
- Reva Schneider
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コンタクト：
- Pramitha Kondancheri
- 電話番号：972-566-3000
- メール：Pramitha.RarothKondancheri@scri.com
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Victoria
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Melbourne、Victoria、オーストラリア、3000
- 募集
- Novartis Investigative Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：INR731 single agent (Arm A)
The dose escalation part with single agent INR731 may be followed by a dose expansion part.
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Oral administration
Background therapy.
Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
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実験的：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.
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Oral administration
Background therapy.
Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Oral administration
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実験的：INR731 in combination with abiraterone (Arm C)
Dose escalation of INR731 in combination with abiraterone.
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Oral administration
Background therapy.
Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Oral administration
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Incidence and severity of dose-limiting toxicities (DLTs)
時間枠：28 days
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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.
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28 days
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Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
時間枠：Up to approximately 24 months
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Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and electrocardiograms (ECGs) qualifying and reported as AEs.
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Up to approximately 24 months
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Frequency of dose interruptions and reductions
時間枠：Up to approximately 24 months
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Number of participants with dose interruptions and/or reductions to assess the tolerability.
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Up to approximately 24 months
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Dose intensity
時間枠：Up to approximately 24 months
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Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
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Up to approximately 24 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Response Rate (ORR)
時間枠：Up to approximately 24 months
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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.
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Up to approximately 24 months
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Disease Control Rate (DCR)
時間枠：Up to approximately 24 months
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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.
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Up to approximately 24 months
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Radiological Progression Free Survival (rPFS)
時間枠：Up to approximately 24 months
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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.
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Up to approximately 24 months
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Prostate-Specific Antigen 50% response rate (PSA50 rate)
時間枠：Up to approximately 24 months
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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.
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Up to approximately 24 months
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Area under the plasma concentration-time curve (AUC) of INR731
時間枠：From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Pharmacokinetic (PK) parameters based on plasma concentrations of INR731.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Maximum plasma concentration (Cmax) of INR731
時間枠：From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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PK parameters based on plasma concentrations of INR731.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Time to reach maximum plasma concentration (Tmax) of INR731
時間枠：From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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PK parameters based on plasma concentrations of INR731.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Trough concentration (Ctrough) of INR731
時間枠：From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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PK parameters based on plasma concentrations of INR731.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Plasma concentrations of study drugs
時間枠：From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Concentration versus time profiles of study drugs.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
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Progression Free Survival (PFS)
時間枠：Up to approximately 24 months
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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.
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Up to approximately 24 months
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2026年5月25日
一次修了 (推定)
2030年6月3日
研究の完了 (推定)
2030年6月3日
試験登録日
最初に提出
2026年4月30日
QC基準を満たした最初の提出物
2026年4月30日
最初の投稿 (実際)
2026年5月6日
学習記録の更新
投稿された最後の更新 (実際)
2026年5月28日
QC基準を満たした最後の更新が送信されました
2026年5月27日
最終確認日
2026年5月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- CINR731A12101
- 2025-524080-20 (レジストリ識別子：EU registry (CTIS))
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
IPD プランの説明
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.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。