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.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Qun Zhao
- Número de teléfono: +8631186095363
- Correo electrónico: zhaoqun@hebmu.edu.cn
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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).
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: 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. |
|
Experimental: 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. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Pathologic Complete Response (pCR) Rate
Periodo de tiempo: 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)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
R0 Resection Rate
Periodo de tiempo: At the time of surgery.
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Proportion of subjects achieving R0 resection evaluated by surgical-pathology report. |
At the time of surgery.
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Event-Free Survival(EFS)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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).
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- MA-GC-II-033
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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