皮下デュルバルマブの薬物動態および安全性を検討する第I相用量漸増・用量拡張試験 (IMFINZI-subQ)
固形腫瘍を有する成人参加者における皮下投与デュルバルマブの薬物動態および安全性を検討する第I相、多施設共同、用量漸増および用量拡張試験
The purpose of the study is to determine a subcutaneous (SC: under the skin) durvalumab + recombinant human hyaluronidase (rHu) dose that yields systemic drug exposure similar to intravenous (IV: into the veins) durvalumab administration and to evaluate the pharmacokinetics and safety of SC durvalumab + rHu injection in participants with different types of solid tumours (cancers).
調査の概要
詳細な説明
This is a Phase I, multicentre study that will consist of 2 parts -
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Part 1 may include participants with solid tumours - non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) or limited-stage small cell lung cancer (LS-SCLC). It will further consist of 2 planned dose levels of SC durvalumab - Dose level 1 (DL1) and Dose level 2 (DL2).
Part 2 will include participants with unresectable HCC. It will be initiated once a dose has been identified based on Part 1.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：AstraZeneca Clinical Study Information Center
- 電話番号：1-877-240-9479
- メール：information.center@astrazeneca.com
研究場所
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Fitzroy、オーストラリア、3065
- 引きこもった
- Research Site
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St Albans、オーストラリア、3021
- 引きこもった
- Research Site
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Woolloongabba、オーストラリア、4102
- 引きこもった
- Research Site
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Batumi、グルジア、6010
- 募集
- Research Site
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Tbilisi、グルジア、0114
- 募集
- Research Site
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Tbilisi、グルジア、0112
- 募集
- Research Site
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Brzozów、ポーランド、36-200
- 募集
- Research Site
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Koszalin、ポーランド、75-581
- 募集
- Research Site
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Lublin、ポーランド、20-090
- 募集
- Research Site
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Olsztyn、ポーランド、10-357
- 募集
- Research Site
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Przemyśl、ポーランド、37-700
- 募集
- Research Site
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Tainan、台湾、73657
- 募集
- Research Site
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Taipei、台湾、112
- 引きこもった
- Research Site
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Taipei、台湾、110
- 募集
- Research Site
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Taoyuan、台湾、333
- 引きこもった
- Research Site
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Seongnam-si、韓国、13620
- 募集
- Research Site
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Seoul、韓国、06351
- 募集
- Research Site
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Seoul、韓国、5505
- 募集
- Research Site
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Seoul、韓国、03722
- 募集
- Research Site
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of ≥ 12 weeks at enrolment.
- Adequate organ and marrow function.
- Minimum body weight > 30 kg.
Part 1 only:
Locally Advanced Unresectable (Stage III) NSCLC Participants -
- Histological or cytological documented evidence of NSCLC (locally advanced, unresectable, Stage III).
- Must have received at least 2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy.
- Have not progressed following definitive concurrent chemoradiation.
LS-SCLC Participants -
- Histologically or cytologically documented LS-SCLC (Stage I-III).
- Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to enrolment.
- Have not progressed following definitive concurrent chemoradiation.
Part 1 and 2:
Unresectable HCC Participants -
- Unresectable HCC based on histopathological confirmation.
- No prior systemic therapy for unresectable HCC.
- Must not be eligible for locoregional therapy for unresectable HCC.
- Child-Pugh Score class A.
- Measurable disease as defined by RECIST v1.1.
Exclusion Criteria:
- Active or prior documented autoimmune disease requiring systemic treatment.
- Uncontrolled infection (including human immunodeficiency virus [HIV], hepatitis B or C).
- Prior exposure to immune checkpoint inhibitors.
Part 1 only:
Locally Advanced Unresectable (Stage III) NSCLC Participants -
- Mixed SCLC and NSCLC histology.
- Active pneumonitis or interstitial lung disease requiring systemic therapy.
LS SCLC Participants -
- Mixed SCLC and NSCLC histology.
- Extensive-stage disease.
- History of Grade ≥ 2 pneumonitis.
Part 1 and 2:
Unresectable HCC Participants -
- Hepatic encephalopathy.
- Uncontrolled ascites.
- Active gastrointestinal (GI) bleeding.
研究計画
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：Part 1: SC Durvalumab DL1
Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
他の名前：
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
|
実験的：Part 1: SC Durvalumab DL2
Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
他の名前：
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
|
実験的：Part 2: Expansion Cohort, SC Durvalumab Dose Level X
Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
他の名前：
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
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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Area under the concentration-time curve
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the AUC of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Observed lowest concentration before the next dose is administered (Ctrough)
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Ctrough of SC durvalumab |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
|
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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Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the AUClast of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Maximum observed concentration (Cmax)
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Cmax of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Time to reach maximum concentration following drug administration (tmax)
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the tmax of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Terminal elimination half-life (t1/2λz)
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the t1/2λz of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Total body clearance/apparent total body clearance (CL[/F])
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the CL(/F) of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Apparent volume of distribution based on the terminal phase volume (Vz[/F])
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the VZ(/F) of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Average drug concentration over a dosing interval (Cavg)
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Cavg of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Serum concentration of durvalumab
時間枠：From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the serum concentration of SC durvalumab at specified timepoints. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Number of participants with adverse events (AEs)
時間枠：Up to Survival Follow-up (approximately 17 months)
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To assess the safety and tolerability of SC durvalumab. |
Up to Survival Follow-up (approximately 17 months)
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Number of participants with dose-limiting toxicities (DLTs)
時間枠：Up to Survival Follow-up (approximately 17 months)
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To assess the safety and tolerability of SC durvalumab. |
Up to Survival Follow-up (approximately 17 months)
|
協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
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
- D907HC00001
- 2025-521639-34-00 (その他の識別子：EU CT number)
- 2025 (米国 NIH グラント/契約)
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?
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
米国FDA規制機器製品の研究
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。