Retlirafusp Alfa or Adebrelimab Plus SOX as Neoadjuvant Therapy for HER2-Negative Resectable Gastric or Gastroesophageal Junction Adenocarcinoma
A Randomized, Exploratory Phase II Study of Retlirafusp Alfa or Adebrelimab Combined With SOX as Neoadjuvant Therapy for HER2-Negative Resectable Gastric or Gastroesophageal Junction Adenocarcinoma
This multicenter, randomized, open-label, exploratory phase II study aims to evaluate the efficacy and safety of perioperative Retlirafusp Alfa plus SOX versus adebrelimab plus SOX in adult patients with previously untreated, HER2-negative, resectable locally advanced gastric or gastroesophageal junction adenocarcinoma (clinical stage II-III, AJCC 8th edition).
Approximately 98 participants will be randomized at a 1:1 ratio via stratified block randomization. Stratification factors include tumor location (gastric versus gastroesophageal junction) and PD-L1 combined positive score (CPS <1 versus CPS ≥1).
Participants will receive 3 preoperative cycles of assigned immunotherapy combined with SOX, followed by D2 radical gastrectomy performed 4-8 weeks after the last neoadjuvant cycle. Postoperatively, participants will receive 5 cycles of the same immunotherapy plus SOX, then up to 9 cycles of immunotherapy monotherapy, with a maximum of 17 total immunotherapy cycles.
The primary outcome measure is pathologic complete response (pCR) rate. Secondary outcome measures include R0 resection rate, event-free survival, disease-free survival, overall survival, surgical safety, adverse events, laboratory abnormalities, and treatment tolerability.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- フェーズ2
連絡先と場所
研究連絡先
研究連絡先
- 名前：Qun Zhao
- 電話番号：+8631186095363
- メール：zhaoqun@hebmu.edu.cn
参加基準
適格基準
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
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Voluntary signed written informed consent.
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Age ≥ 18 years.
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Histologically-confirmed gastric / gastroesophageal junction adenocarcinoma; Siewert II / III are eligible.
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Resectable clinical stage II-III (cT1-2N+M0, cT3-4aNanyM0, AJCC 8th edition) confirmed by CT / MRI.
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No prior anti-cancer therapy (surgery, radiotherapy, chemotherapy, targeted or immunotherapy).
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Investigator-assessable for R0 resection; planned curative surgery after neoadjuvant therapy.
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Able to swallow oral tablets.
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ECOG-PS 0-1.
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Available PD-L1 CPS result or 3-5 unstained tumor slides for testing (fresh or pre-randomization FFPE tissue acceptable).
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Estimated life expectancy ≥ 12 months.
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Adequate organ function (no transfusion / G-CSF in prior 14 d):
- ANC ≥ 1.5 × 10⁹/L; platelets ≥ 80 × 10⁹/L; Hb ≥ 90 g/L
- Total bilirubin < 1.5 × ULN; ALT/AST ≤ 2.5 × ULN
- Serum Cr ≤ 1.5 × ULN or CrCl > 50 mL/min
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Women of child-bearing potential: negative serum pregnancy test ≤ 72 h pre-randomization; effective contraception (longer of 3 months post-last retlirafusp alfa / adebrelimab or 6 months post-chemotherapy). Fertile-partner males: surgical sterility or same contraception window; no sperm donation during study.
Exclusion Criteria
- Known HER2-positive tumor.
- Anticipated transthoracic surgical approach.
- Unresectable disease, surgical contraindication or refusal of surgery.
- Other malignancy within 5 years (exception: cured basal-cell skin, cervical / breast carcinoma-in-situ).
- Laparoscopy shows peritoneal metastasis, positive peritoneal cytology (CY1P0) or AJCC 8th T4b disease.
- Cardiac abnormalities: NYHA ≥ II heart failure or LVEF < 50 %; unstable angina; MI within 1 year; QTc prolongation (male>450 ms, female>470 ms); significant ECG abnormality / high-grade AV-block / PR>250 ms; risk factors for QTc prolongation.
- Gastrointestinal obstruction signs/symptoms within prior 6 months (except symptoms resolved by definitive surgery).
- Coagulopathy (INR>2.0, PT>16 s), bleeding diathesis or ongoing thrombolytic / anticoagulant therapy (prophylactic low-dose aspirin / LMWH allowed).
- Clinically-significant bleeding tendency within 3 months pre-randomization. Persistently positive fecal occult blood requires gastroscopy.
- GI perforation or fistula within prior 6 months.
- Arterial / venous thromboembolic event within prior 6 months (superficial phlebothrombosis excluded).
- Hereditary / acquired bleeding or thrombotic diathesis.
- Active ulcer, unhealed wound or fracture.
- Major vascular disease within prior 6 months.
- CTCAE>grade 2 severe infection within 4 weeks pre-randomization; active pulmonary inflammation; ongoing need for systemic antibiotics (≤48 h prophylactic IV antibiotics permitted).
- Active hepatitis B (HBsAg+ plus HBV-DNA ≥ 2000 IU/mL) or active hepatitis C.
- Congenital / acquired immunodeficiency including HIV infection.
- Prior or planned organ / allogeneic bone-marrow transplantation.
- Interstitial lung disease / pneumonitis (current or steroid-treated history); pulmonary fibrosis, pneumoconiosis, active tuberculosis or severe pulmonary impairment on screening CT.
- Active autoimmune disease or high-risk relapse history (exceptions: hormone-replaced hypothyroidism; controlled type 1 diabetes; stable vitiligo, psoriasis, resolved childhood asthma; asthma requiring bronchodilators is excluded).
- Systemic immunosuppressive corticosteroids (>10 mg prednisone-equivalent daily) within 7 days pre-randomization.
- Live-attenuated vaccine within 28 days pre-randomization or planned during-/within 60 days post-study-treatment.
- Hypersensitivity to any study drug or excipients.
- Investigational-drug clinical trial participation within prior 4 weeks.
- Pregnancy, lactation or planned pregnancy during study treatment.
- Investigator-judged other conditions interfering with study conduct or participant safety (substance abuse, severe psychiatric illness etc).
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：並列代入
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的：Retlirafusp Alfa Plus SOX
Retlirafusp alfa plus SOX for 3 preoperative 21-day cycles, followed by D2 radical surgery, then retlirafusp alfa plus SOX for 5 postoperative cycles, followed by retlirafusp alfa alone for 9 cycles. Retlirafusp alfa may be given for a maximum of 17 cycles in total. |
1800 mg administered by intravenous infusion on Day 1 of each 21-day cycle. Given with SOX for 3 preoperative and 5 postoperative cycles, then as monotherapy for 9 cycles, up to 17 cycles in total. When administered with oxaliplatin, retlirafusp alfa is infused first, with an interval of at least 30 minutes before oxaliplatin. |
|
実験的：Adebrelimab Plus SOX
Adebrelimab plus SOX for 3 preoperative 21-day cycles, followed by D2 radical surgery, then adebrelimab plus SOX for 5 postoperative cycles, followed by adebrelimab alone for 9 cycles. Adebrelimab may be given for a maximum of 17 cycles in total. |
1200 mg administered by intravenous infusion on Day 1 of each 21-day cycle. Given with SOX for 3 preoperative and 5 postoperative cycles, then as monotherapy for 9 cycles, up to 17 cycles in total. When administered with oxaliplatin, adebrelimab is infused first, with an interval of at least 30 minutes before oxaliplatin. |
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Pathologic Complete Response (pCR) Rate
時間枠：After D2 radical surgery (within 8 weeks after neoadjuvant completion)
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Proportion of participants achieving TRG0 (CAP criteria): no viable tumor cells in primary tumor and regional lymph nodes after neoadjuvant therapy. Evaluated on surgical resection specimen. |
After D2 radical surgery (within 8 weeks after neoadjuvant completion)
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
R0 Resection Rate
時間枠：At the time of surgery.
|
Proportion of subjects achieving R0 resection evaluated by surgical-pathology report. |
At the time of surgery.
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Event-Free Survival(EFS)
時間枠：Up to 5 years from randomization.
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Time from randomization to disease progression, recurrence or death from any cause (whichever occurs first). |
Up to 5 years from randomization.
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Disease-Free Survival(DFS)
時間枠：Up to 5 years after surgery.
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For post-surgery subjects without residual disease: time from surgery to disease recurrence or death from any cause. |
Up to 5 years after surgery.
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Overall Survival(OS)
時間枠：Up to 5-year follow-up post-randomization.
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Time from randomization to death from any cause. |
Up to 5-year follow-up post-randomization.
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Safety and Tolerability
時間枠：From first study drug dose to safety-follow-up completion (90 days after last immunotherapy or 30 days post-chemotherapy/surgery, whichever occurs later).
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Incidence, severity (CTCAE v6.0) of adverse events(AE), serious adverse events(SAE); surgical-related complications; treatment-related dose modification/discontinuation rate. |
From first study drug dose to safety-follow-up completion (90 days after last immunotherapy or 30 days post-chemotherapy/surgery, whichever occurs later).
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
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
最終確認日
詳しくは
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