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進行性／転移性相同組換え欠損固形癌患者を対象としたAZD4956単剤療法および抗がん剤との併用療法に関する研究 (PARTHENON)

2026年10月26日 更新者：AstraZeneca

先進的/転移性相同組換え修復欠損固形腫瘍を有する参加者において、単剤療法および抗がん剤との併用療法として、AZD4956の漸増投与量の安全性、忍容性、薬物動態、薬力学、および予備的有効性を評価するモジュラー式オープンラベル第I/IIa相試験

The purpose of this modular, first trial in human study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of ascending dose levels (DLs) of AZD4956 monotherapy and in combination with other anti-cancer agents in participants with advanced/metastatic solid tumours with homologous recombination repair (HRR) deficiencies.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

The study consists of individual modules each evaluating the safety and tolerability of AZD4956 dosed as monotherapy, or with a specific combination partner. There are following 2 modules -

  1. Module 1: AZD4956 monotherapy
  2. Module 2: AZD4956 in combination with saruparib

Each module may further contain 2 parts-

  • Part A (dose escalation/dose finding): To determine the safety, tolerability, PK, PD, and preliminary efficacy of AZD4956 as monotherapy or in combination.
  • Part B (dose expansion): To further evaluate the safety and preliminary efficacy of AZD4956 in combination with other anti-cancer agents.

研究の種類

介入

入学 (推定)

180

段階

  • フェーズ2
  • 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

研究場所

  • アメリカ
    • New York
      • New York、New York、アメリカ、10065
        • 募集
        • Research Site
    • Rhode Island
      • Providence、Rhode Island、アメリカ、02903
        • 募集
        • Research Site
    • Texas
      • Houston、Texas、アメリカ、77030
        • 募集
        • Research Site
    • Virginia
      • Fairfax、Virginia、アメリカ、22031
        • 募集
        • Research Site
  • イギリス
      • Cambridge、イギリス、CB2 0QQ
        • 募集
        • Research Site
      • London、イギリス、SE1 9RT
        • まだ募集していません
        • Research Site
      • Sutton、イギリス、SM25PT
        • 募集
        • Research Site
  • オーストラリア
      • Melbourne、オーストラリア、3000
        • 募集
        • Research Site
      • Westmead、オーストラリア、2145
        • 募集
        • Research Site
  • スペイン
      • Barcelona、スペイン、08036
        • 募集
        • Research Site
      • Barcelona、スペイン、8035
        • まだ募集していません
        • Research Site
      • Barcelona、スペイン、08023
        • 募集
        • Research Site
      • Logroño、スペイン、26006
        • まだ募集していません
        • Research Site
      • Pozuelo de Alarcón、スペイン、28223
        • まだ募集していません
        • Research Site
      • Seville、スペイン、41013
        • まだ募集していません
        • Research Site
  • 日本
      • Chūōku、日本、104-0045
        • 募集
        • Research Site
      • Kashiwa、日本、277-8577
        • 募集
        • Research Site
  • 韓国
      • Seoul、韓国、03080
        • 募集
        • Research Site
      • Seoul、韓国、120-752
        • 募集
        • Research Site

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

18年～130年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Core Inclusion Criteria:

  • Documented locally advanced or metastatic solid tumour malignancy.
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to screening and first day of dosing.
  • Minimum life expectancy ≥ 12 weeks.
  • Adequate organ and marrow function.
  • Female participants must not breastfeed and must not donate or retrieve ova for their own use from screening to approximately 6 months after the last dose of study intervention.

Module 1 Inclusion Criteria:

  • Demonstrated evidence of disease progression.
  • Participants must have advanced or metastatic solid tumours.
  • Participants may have received up to one prior line of therapy with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)-based regimen (either as a treatment or as maintenance).

Module 2 Inclusion Criteria:

Part A (AZD4956 in Combination with Saruparib Dose Escalation) and Part A-PD (PD Backfill Cohorts):

  • Participants must have one of the following conditions-

    1. Histologically or cytologically confirmed carcinoma of the breast with recurrent locally advanced or metastatic disease and evidence of a predicted loss of function germline or somatic mutation.
    2. Histologically or cytologically confirmed advanced ovarian, fallopian tube, or primary peritoneal cancer.
    3. Histologically or cytologically confirmed adenocarcinoma of the prostate and advanced/metastatic castrate resistant prostate cancer (CRPC).
    4. Histologically or cytologically confirmed advanced/metastatic pancreatic cancer.

  • Participants must have evaluable disease.

  • Participants in PD backfill cohorts must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).

Part A (PD Backfill Cohorts) - Participants Undergoing Paired Biopsies:

- Participants must have a tumour suitable for biopsy.

Part A-Non-PD (Non-PD Backfill Cohorts) and Part B (Dose Expansion Cohorts):

  • Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and advanced/metastatic CRPC.
  • Participants must have documented metastatic disease by clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or ≥ 1 soft tissue lesion (measurable or non-measurable).
  • Participants must have received the prior approved systemic therapies for metastatic prostate cancer.
  • Participants must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).

Core Exclusion Criteria:

  • Any significant laboratory finding or any severe and uncontrolled medical condition.
  • Participants with any known predisposition to bleeding.
  • Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.
  • Allogenic organ transplantation.
  • Known to have active infection, including hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • Known history of infection with human immunodeficiency virus (HIV).
  • Active gastrointestinal disease or other condition that will interfere significantly with the swallowing, absorption, distribution, metabolism or excretion of oral therapy.
  • Participants with history of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
  • Participants with a known hypersensitivity to the investigational product(s) or any of the excipients of the product(s).
  • Previous dosing with AZD4956.

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：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
実験的：Module 1 Part A: AZD4956 monotherapy (Dose escalation)

Participants will receive AZD4956 as monotherapy at ascending dose levels.
薬：AZD4956

AZD4956 will be administered orally.
実験的：Module 2 Part A: AZD4956 + saruparib (Dose escalation)

Participants will receive AZD4956 at ascending dose levels in combination with saruparib.
薬：Saruparib

Saruparib will be administered orally.

薬：AZD4956

AZD4956 will be administered orally.
実験的：Module 2 Part A Optional PD backfill cohort: AZD4956 + saruparib

Participants will receive AZD4956 in combination with saruparib.
薬：Saruparib

Saruparib will be administered orally.

薬：AZD4956

AZD4956 will be administered orally.
実験的：Module 2 Part A Optional PD backfill cohort: Saruparib monotherapy

Participants will receive saruparib monotherapy.
薬：Saruparib

Saruparib will be administered orally.
実験的：Module 2 Part A Optional non-PD backfill cohort: AZD4956 + saruparib

Participants with metastatic castrate resistant prostate cancer (mCRPC) will receive AZD4956 in combination with saruparib.
薬：Saruparib

Saruparib will be administered orally.

薬：AZD4956

AZD4956 will be administered orally.
実験的：Module 2 Part B: AZD4956 + saruparib (Dose expansion)

Participants will receive AZD4956 in combination with saruparib.
薬：Saruparib

Saruparib will be administered orally.

薬：AZD4956

AZD4956 will be administered orally.

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
Parts A and B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
時間枠：From Screening (Day -28) to follow-up (up to 3.5 years)

To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s).
From Screening (Day -28) to follow-up (up to 3.5 years)
Part B: Progression free survival (PFS)
時間枠：Up to 3.5 years

PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression.
Up to 3.5 years
Part A - Number of participants with dose-limiting toxicities (DLTs)
時間枠：Up to 28 days

To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s).
Up to 28 days

二次結果の測定

結果測定
メジャーの説明
時間枠
Objective response (OR)
時間枠：Up to 3.5 years

OR is defined as if a participant achieves a best overall response (BOR) of confirmed complete response (CR) or partial response (PR), as assessed by the investigator, according to response evaluation criteria in solid tumours (RECIST) v1.1 criterion.
Up to 3.5 years
Duration of response (DoR)
時間枠：Up to 3.5 years

DoR is defined as the time from the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by prostate cancer working group 3 (PCWG3), until the date of documented disease progression or death in the absence of disease progression.
Up to 3.5 years
Best Overall Response (BOR)
時間枠：Up to 3.5 years

To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer agent(s).
Up to 3.5 years
Time to response (TTR)
時間枠：Up to 3.5 years

TTR is defined as the time from the date of first dose of study intervention until the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, which is subsequently confirmed.
Up to 3.5 years
Disease control (DC)
時間枠：Up to 3.5 years

DC is defined as if a participant has achieved a best OR of confirmed CR or PR or SD as BOR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3.
Up to 3.5 years
Clinical benefit rate (CBR)
時間枠：Up to 3.5 years

CBR is defined as the percentage of advanced cancer participants who achieve CR, PR, or at least 16 weeks/24 weeks of stable disease, assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, as a result of therapy.
Up to 3.5 years
Part A: Progression free survival (PFS)
時間枠：Up to 3.5 years

PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression.
Up to 3.5 years
Percentage change from baseline in tumour size
時間枠：Up to 3.5 years

The best percentage change from baseline in target lesion (TL) tumour size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments.
Up to 3.5 years
Number of participants with cancer antigen 125 (CA125) response (for ovarian cancer participants)
時間枠：From baseline up to 3.5 years

CA125 response is defined as if at least a 50% reduction in CA125 levels from a pre-treatment sample.
From baseline up to 3.5 years
Radiological progression free survival (rPFS) (for prostate cancer participants)
時間枠：Up to 3.5 years

PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression.
Up to 3.5 years
Change from baseline in prostate specific antigen 50 (PSA50) response rate (for prostate cancer participants)
時間枠：From baseline up to 3.5 years

PSA50 response is defined as if a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later has been achieved.
From baseline up to 3.5 years
Change from baseline in PSA90 response rate (for prostate cancer participants)
時間枠：From baseline up to 3.5 years

PSA90 response is defined as if a ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later has been achieved.
From baseline up to 3.5 years
Change from baseline in PSA undetectable rate
時間枠：At 3, 6 and 9 months

Undetectable PSA is defined as a measurement of < 0.2 ng/mL.
At 3, 6 and 9 months
Time to PSA50/90 response (for prostate cancer participants)
時間枠：Up to 3.5 years

Time to PSA50/90 response is defined as the time from the date of first dose of study intervention until the date of first documented PSA response (≥ 50%/90% decrease in PSA from baseline) that is confirmed by a second consecutive PSA assessment at least 3 weeks later.
Up to 3.5 years
Time to PSA progression (for prostate cancer participants)
時間枠：Up to 3.5 years

Time to PSA progression is defined as the time from date of first dose of study intervention until the date of first documented PSA progression or the last PSA result in the absence of progression.
Up to 3.5 years
PSA PFS at 6 months (PSA-6)
時間枠：At 6 months

PSA progression is defined as an increase in PSA of ≥ 25% from the nadir and an absolute increase of at least 2 ng/mL above nadir beyond 12 weeks. To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer. agent(s)
At 6 months
Area under the concentration-time curve (AUC)
時間枠：From date of first dose of study intervention up to 59 days after first dose

To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).
From date of first dose of study intervention up to 59 days after first dose
Maximum concentration (Cmax)
時間枠：From date of first dose of study intervention up to 59 days after first dose

To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).
From date of first dose of study intervention up to 59 days after first dose
Time to maximum concentration (Tmax)
時間枠：From date of first dose of study intervention up to 59 days after first dose

To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).
From date of first dose of study intervention up to 59 days after first dose
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe(t1-t2))
時間枠：From date of first dose of study intervention up to 16 days after first dose

To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).
From date of first dose of study intervention up to 16 days after first dose
Renal clearance (CLR)
時間枠：From date of first dose of study intervention up to 16 days after first dose

To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).
From date of first dose of study intervention up to 16 days after first dose
Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 (Ae(t1-t2))
時間枠：From date of first dose of study intervention up to 16 days after first dose

To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).
From date of first dose of study intervention up to 16 days after first dose
Change in amount of KRAB-associated protein-1 phosphorylated on serine 824 [pKAP1 (Ser824)] biomarker in tumour cells at baseline and during treatment
時間枠：From Baseline up to 3.5 years

To evaluate PD of AZD4956 in tumour cells when given orally as monotherapy and in combination with anti-cancer agent(s).
From Baseline up to 3.5 years

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

AstraZeneca

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3月17日

一次修了 (推定)

2030年3月29日

研究の完了 (推定)

2030年3月29日

試験登録日

最初に提出

2026年2月26日

QC基準を満たした最初の提出物

2026年2月26日

最初の投稿 (実際)

2026年3月3日

学習記録の更新

投稿された最後の更新 (実際)

2026年10月27日

QC基準を満たした最後の更新が送信されました

2026年10月26日

最終確認日

2026年10月1日

詳しくは

本研究に関する用語

キーワード

その他の研究ID番号

  • D8570C00001
  • 2025 (米国 NIH グラント/契約)
  • 2025-524171-22-00 (レジストリ識別子：CTIS (EU))

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?

はい

IPD プランの説明

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD 共有時間枠

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD 共有アクセス基準

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

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。

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