Intratumoral Injection of Recombinant Human Endostatin Adenovirus (EDS01) for the Treatment of Recurrent or Metastatic Head and Neck Tumors (EDS01 HN)
A Phase I Clinical Trial of Intratumoral Injection of Recombinant Human Endostatin Adenovirus (EDS01) Combined With Toripalimab for the Treatment of Recurrent or Metastatic Head and Neck Tumors
This single-center, Phase 1 study is evaluating the safety, tolerability, and preliminary antitumor activity of recombinant human endostatin adenovirus injection (EDS01) given by intratumoral injection in combination with toripalimab in adults with recurrent or metastatic head and neck tumors, including nasopharyngeal carcinoma, whose disease has progressed after platinum-based systemic therapy or who are not suitable for further platinum treatment.
A total of 9 participants will be enrolled in 3 planned dose groups of EDS01. EDS01 will be injected directly into an accessible tumor lesion on Days 0 and 7, and toripalimab 240 mg will be administered intravenously on Day 1 of each treatment cycle for up to 4 cycles, unless disease progression or unacceptable toxicity occurs. The study will evaluate treatment-related adverse events as well as preliminary efficacy outcomes, including tumor response, disease control, and time to progression, using clinical assessments, laboratory tests, imaging, and follow-up after treatment.
調査の概要
状態
条件
詳細な説明
Patients with recurrent or metastatic head and neck tumors, including nasopharyngeal carcinoma, have limited treatment options after failure of platinum-based therapy. Anti-programmed cell death protein 1 (PD-1) therapy is an established later-line treatment option in this setting. EDS01 is a recombinant human endostatin adenovirus injection designed for intratumoral administration. By delivering the human endostatin gene into tumor cells, EDS01 is intended to support sustained local expression of endostatin and inhibit tumor angiogenesis. Head and neck lesions are often accessible for direct intratumoral injection and serial local assessment, which makes this disease setting suitable for evaluation of this approach. Prior early-phase clinical experience with EDS01 in advanced head and neck tumors showed that the main observed toxicities were fever, injection-site pain, and flu-like symptoms, without dose-limiting toxicity or serious adverse events at the studied dose levels, and preliminary antitumor activity was observed. These findings support further evaluation of EDS01 in combination with PD-1 blockade.
This single-center Phase 1 study is designed to evaluate the safety, tolerability, and preliminary antitumor activity of EDS01 in combination with toripalimab in adults with recurrent or metastatic head and neck tumors who have previously received platinum-based treatment or demonstrated platinum insensitivity or intolerance, and who have an injectable tumor lesion. The study will explore planned EDS01 dose levels in combination with fixed-dose toripalimab in order to characterize the safety profile of the regimen and identify whether the combination is feasible for further clinical development.
Study evaluations include clinical assessments, physical examinations, laboratory testing, and monitoring of adverse events and serious adverse events. Tumor response will be assessed radiographically according to RECIST version 1.1, including evaluation of objective response, disease control, and time to progression. Additional translational and exploratory assessments include anti-adenovirus antibody testing, serum endostatin measurement, and selected monitoring related to environmental shedding after intratumoral administration. After treatment, participants will enter follow-up and be assessed every 3 months until disease progression or death.
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：nan lin, MD
- 電話番号：+8618708305692
- メール：nanishard@gmail.com
研究場所
-
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China
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Chengdu、China、中国、610041
- 募集
- West China Hospital
-
コンタクト：
- Xuelei Ma
- 電話番号：18708305692
- メール：drmaxuelei@gmail.com
-
-
参加基準
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
説明
Inclusion Criteria:
Adults aged 18 to 65 years. Histologically or cytologically confirmed recurrent or metastatic head and neck tumor.
Previously received at least 1 standard platinum-based systemic chemotherapy regimen for recurrent/metastatic disease, or had platinum-insensitive or platinum-intolerant disease after prior curative-intent treatment.
Not suitable for surgery or radiotherapy. At least 1 target lesion suitable for intratumoral injection of recombinant human endostatin adenovirus injection.
At least 1 measurable lesion with diameter ≥2 cm on imaging, according to RECIST version 1.1.
No chemotherapy, radiotherapy, biologic antitumor therapy, or antiviral therapy within 4 weeks before enrollment.
Estimated life expectancy of at least 12 weeks. ECOG performance status 0 to 1. Male or female participants of childbearing potential must agree to use reliable contraception during treatment and for at least 6 months after treatment.
Recovery of prior treatment-related toxicities to NCI CTCAE grade 1 or baseline, with screening laboratory results within 1 week before enrollment meeting protocol requirements: ANC ≥1.5×10^9/L, platelet count ≥80×10^9/L, total bilirubin ≤1.5 × ULN, ALT and AST ≤2 × ULN, and coagulation parameters ≤1.25 × ULN.
Willing and able to provide written informed consent.
Exclusion Criteria:
Known allergy to the study drugs. Lesions involving major blood vessels or nerves and therefore unsuitable for local injection.
Receiving radiotherapy to the study lesion at the same time. Prior anti-angiogenic therapy. Receiving immunosuppressive therapy or systemic corticosteroids for immunosuppressive purposes at a dose greater than prednisone 10 mg/day (or equivalent) within 2 weeks before enrollment.
Active autoimmune disease or history of autoimmune disease. Congenital or acquired immunodeficiency. Risk of major nasopharyngeal hemorrhage or deep nasopharyngeal ulceration. Severe coagulation disorder or bleeding tendency. Severe uncontrolled medical disease or myocardial infarction within 3 months before enrollment.
Acute infection. Pregnant or breastfeeding women. Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.
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 |
|---|---|
|
実験的：EDS01 1.0×10^11 VP + Toripalimab
Participants receive intratumoral EDS01 1.0×10^11 viral particles (VP) on Days 0 and 7 plus toripalimab 240 mg by intravenous infusion on Day 1 of each 21-day cycle.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
Recombinant human endostatin adenovirus injection (EDS01) is administered by intratumoral injection into an accessible tumor lesion on Days 0 and 7 of each 21-day cycle.
Three planned dose levels are evaluated across study cohorts: 1.0×10^11 VP.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
|
実験的：EDS01 5.0×10^11 VP + Toripalimab
Participants receive intratumoral EDS01 5.0×10^11 viral particles (VP) on Days 0 and 7 plus toripalimab 240 mg by intravenous infusion on Day 1 of each 21-day cycle.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
Recombinant human endostatin adenovirus injection (EDS01) is administered by intratumoral injection into an accessible tumor lesion on Days 0 and 7 of each 21-day cycle.
Three planned dose levels are evaluated across study cohorts: 5.0×10^11 VP.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
|
実験的：EDS01 1.0×10^12 VP + Toripalimab
Participants receive intratumoral EDS01 1.0×10^12 viral particles (VP) on Days 0 and 7 plus toripalimab 240 mg by intravenous infusion on Day 1 of each 21-day cycle.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
Recombinant human endostatin adenovirus injection (EDS01) is administered by intratumoral injection into an accessible tumor lesion on Days 0 and 7 of each 21-day cycle.
Three planned dose levels are evaluated across study cohorts: 1.0×10^12 VP.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
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 |
|---|---|---|
|
Incidence of adverse events (AEs) and serious adverse events (SAEs)
時間枠：From signing informed consent through 1 month after the end of treatment (up to 16 weeks).
|
Number and percentage of participants with adverse events (AEs), serious adverse events (SAEs), treatment-related adverse events, and clinically significant abnormal laboratory findings.
Adverse events will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC), version 4.0.
Safety evaluation will also include physical examination findings and environmental shedding monitoring related to intratumoral administration of EDS01.
|
From signing informed consent through 1 month after the end of treatment (up to 16 weeks).
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective response rate of target lesions
時間枠：From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
|
Proportion of participants with complete response (CR) or partial response (PR) in target lesions.
Tumor response will be assessed according to RECIST version 1.1.
|
From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
|
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Disease control rate of target lesions
時間枠：From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
|
Proportion of participants with complete response (CR), partial response (PR), or stable disease (SD) in target lesions, assessed according to RECIST version 1.1.
|
From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
|
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Overall objective response rate of all lesions
時間枠：From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
|
Proportion of participants with complete response (CR) or partial response (PR) in overall lesions, assessed according to RECIST version 1.1.
|
From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Time to progression (TTP)
時間枠：From enrollment until first documented disease progression; participants will be followed every 3 months after treatment until progression or death. Up to 3 years from enrollment.
|
Time from enrollment to the first documented disease progression.
Deaths before progression will be censored.
|
From enrollment until first documented disease progression; participants will be followed every 3 months after treatment until progression or death. Up to 3 years from enrollment.
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in serum anti-adenovirus IgG
時間枠：From signing informed consent through 1 month after the end of treatment (up to approximately 16 weeks).
|
Change in serum anti-adenovirus (ADV) IgG from baseline to post-baseline assessments, measured by ELISA.
|
From signing informed consent through 1 month after the end of treatment (up to approximately 16 weeks).
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協力者と研究者
スポンサー
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
その他の研究ID番号
- 2025(395)
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 共有サポート情報タイプ
- STUDY_PROTOCOL
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