HLA-A*02:01 および TP53 R175H 変異陽性の切除不能な進行性および/または転移性固形腫瘍を有する成人被験者における NT-175 の研究
切除不能な進行性および/または転移性固形腫瘍を有するヒト白血球抗原-A*02:01陽性成人被験者におけるNT-175の安全性と予備抗腫瘍活性を評価する非盲検第1相多施設共同研究TP53 R175H 変異陽性
Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies
調査の概要
状態
介入・治療
詳細な説明
This is a Phase 1, open-label, multicentre platform study to evaluate the safety and preliminary antitumour activity of NT-175 in HLA-A*02:01 participants with advanced malignancies that are positive for the TP53 R175H mutation.
Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D.
Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at or below the MTD in disease specific histologies and determine the RP2D.
Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of NT-175 at the RP2D in disease specific settings.
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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Arizona
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Gilbert、Arizona、アメリカ、85234
- 募集
- Research Site
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California
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Duarte、California、アメリカ、91010
- 募集
- Research Site
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Los Angeles、California、アメリカ、90095
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- Research Site
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Newport Beach、California、アメリカ、92663
- 募集
- Research Site
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Santa Monica、California、アメリカ、90404
- 募集
- Research Site
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Florida
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Jacksonville、Florida、アメリカ、32224
- 募集
- Research Site
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Miami、Florida、アメリカ、33136
- 引きこもった
- Research Site
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Tampa、Florida、アメリカ、33612
- 引きこもった
- Research Site
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- 募集
- Research Site
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Boston、Massachusetts、アメリカ、02115
- 募集
- Research Site
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New Jersey
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New Brunswick、New Jersey、アメリカ、08901
- 募集
- Research Site
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New York
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New York、New York、アメリカ、10065
- 募集
- Research Site
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North Carolina
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Charlotte、North Carolina、アメリカ、28204
- 引きこもった
- Research Site
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Winston-Salem、North Carolina、アメリカ、27103
- 引きこもった
- Research Site
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Oregon
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Portland、Oregon、アメリカ、97213
- 募集
- Research Site
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- 募集
- Research Site
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- 募集
- Research Site
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Texas
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Houston、Texas、アメリカ、77030
- 募集
- Research Site
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Round Rock、Texas、アメリカ、78665
- 募集
- Research Site
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Wisconsin
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Milwaukee、Wisconsin、アメリカ、53226
- 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
Key Inclusion Criteria (Module 1)
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Subjects must be at least 18 years of age
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Subject must be diagnosed with one of the histologies below:
- NSCLC
- Colorectal adenocarcinoma
- HNSCC
- Pancreatic adenocarcinoma
- Breast cancer
- Ovarian cancer
- Any other solid tumor
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Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A*02:01 positive (at least 1 allele)
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Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
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Subject has at least 1 measurable lesion
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
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Adequate hematological, renal, hepatic, pulmonary, and cardiac function
Key Exclusion Criteria (Module 1)
- Any another primary malignancy within the 3 years prior to enrollment
- Known, active primary central nervous system (CNS) malignancy
- History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
- History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
- Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
- Any form of primary immunodeficiency.
- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
Key Inclusion Criteria (Module 2 - hematological malignancies)
- At least 18 years of age
- Diagnosis of AML or MDS that allows for efficacy assessments
- Confirmation of TP53 R175H variant mutation in cancer cells
- Subject must be HLA-A*02:01 positive (at least 1 allele)
- ECOG performance status of 0 to 1
Key Exclusion Criteria (Module 2 - hematological malignancy)
- Acute promyelocytic leukaemia or isolated extramedullary disease
- Another primary malignancy within 2 years (with exceptions)
- HSCT within 100 days or immunosuppression for GvHD within 4 weeks
- History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells
- Prior stroke, ischemic attack, significant cardiac disease, heart failure
- Prior adoptive modified cell therapy
- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
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：非ランダム化
- 介入モデル：単一グループの割り当て
- 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：NT-175 for advanced malignancies
TCR T cell therapy product |
|
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 |
|---|---|---|
|
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
時間枠：28 days after infusion
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Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175 |
28 days after infusion
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Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
時間枠：Up to 24 months post-infusion
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Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE) |
Up to 24 months post-infusion
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Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
時間枠：Up to 24 months after infusion
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Per RECIST v1.1 determined by Investigator assessment:
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Up to 24 months after infusion
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Module 2: Safety of NT-175 in participants with haematological malignancies
時間枠：Up to 28 days after infusion
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- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175 |
Up to 28 days after infusion
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Module 2: Safety of NT-175 in participants with haematological malignancies
時間枠：Up to 24 months after infusion
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Up to 24 months after infusion
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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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Module 1, Part 1: Preliminary anti-tumor activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
時間枠：Up to 24 months after infusion
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Per RECIST v1.1 determined by Investigator assessment:
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Up to 24 months after infusion
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Module 2: Evaluate preliminary anti-tumour activity in participants with AML or MDS
時間枠：Up to 24 months after infusion
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Per ELN 2022 criteria for AML and per IWG 2023 criteria for MDS by Investigator assessment:
By Investigator assessment:
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Up to 24 months after infusion
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協力者と研究者
スポンサー
捜査官
- スタディディレクター：AstraZeneca、AstraZeneca
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
追加の関連 MeSH 用語
その他の研究ID番号
- NT-175-201
- D8690C00001 (その他の識別子：AstraZeneca)
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。