A Single-Arm Study of QL1706 Combined With DOS as Neoadjuvant Therapy for Locally Advanced Gastric/GEJ Adenocarcinoma
A Single-Arm, Prospective, Open-Label Clinical Study of Iparomlimab and Tuvonralimab (QL1706) Combined With DOS as Neoadjuvant Therapy for Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Tipo de estudo
Tipo de estudo
Inscrição (Estimado)
Inscrição
Estágio
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
Contato de estudo
- Nome: Yongxu Jia
- Número de telefone: 66271157
- E-mail: jiayongxu111@126.com
Locais de estudo
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Henan
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Zhengzhou, Henan, China, 450000
- The First Affiliated Hospital of Zhengzhou University
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Contato:
- Yongxu Jia
- Número de telefone: 66271157
- E-mail: jiayongxu111@126.com
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Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Aged 18 to 75 years; male or female.
- Previously untreated, resectable adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
- Clinical stage cT3-4a/N+ M0.
- ECOG performance status 0-1.
- Adequate organ function within 7 days prior to treatment, meeting the following criteria: (1) Complete blood count (CBC) criteria (without blood transfusion within 14 days): Hemoglobin (Hb) ≥ 90 g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 80 × 10⁹/L; (2) Serum chemistry criteria: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 60 mL/min; (3) Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%). (4) Thyroid function: thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN).
- Participants of childbearing potential must agree to use effective contraception during the study period and for 6 months after study completion.
- The participant voluntarily agrees to participate in this study and signs the informed consent form.
Exclusion Criteria:
- Known history of hypersensitivity or allergy to QL1706 or its excipients, tegafur/gimeracil/oteracil (S-1), oxaliplatin, docetaxel, or any of their excipients.
- History of another malignancy within 5 years prior to screening or concurrent malignancy, except for curatively treated carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder tumors.
- Patients with distant metastasis and/or unresectable disease;
- Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents.
- Receipt of any antineoplastic agents within 4 weeks prior to the first dose of study drug.
- Patients with gastrointestinal disorders such as intestinal obstruction (including partial obstruction), or those with evidence or risk of gastrointestinal bleeding, perforation, or obstruction.
- Any bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to enrollment, or unhealed wounds, ulcers, or fractures.
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.
- Subjects requiring systemic therapy with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose of study drug.
- Receipt of live or live-attenuated vaccine within 4 weeks prior to the first dose of study drug.
- Major surgery or significant trauma within 4 weeks prior to the first dose of study drug.
- Active or history of autoimmune disease, with the exception of vitiligo or resolved childhood asthma/atopy that requires no intervention in adulthood.
- History of immunodeficiency, including HIV infection, or other acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation.
- Subjects with inadequately controlled cardiovascular clinical symptoms or diseases.
- Severe infection (CTCAE Grade > 2) within 4 weeks prior to the first dose of study drug.
- Patients with a history of interstitial lung disease (except for radiation pneumonitis not treated with corticosteroids), non-infectious pneumonitis, or active pulmonary tuberculosis; or a history of active pulmonary tuberculosis within 1 year prior to enrollment, or more than 1 year prior to enrollment if not adequately treated.
- Pregnant or breastfeeding women.
- Other concomitant diseases that, in the opinion of the Investigator, pose a serious risk to the subject's safety or may interfere with the subject's ability to complete the study.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
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Experimental: Iparomlimab and Tuvonralimab Injection (QL1706) Plus DOS Neoadjuvant Therapy Arm
Enrolled patients receive QL1706 (5 mg/kg, IV, D1) combined with the DOS regimen (docetaxel 40 mg/m², IV, D1 + oxaliplatin 100 mg/m², IV, D1 + S-1 40 mg/m², PO, BID, D1-14), administered every 21 days per cycle for 3-4 cycles.
Subjects who complete neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy, followed by subsequent treatment based on postoperative pathological assessment.
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5 mg/kg, intravenous infusion, administered once every 21 days (D1), for 3-4 cycles.
Outros nomes:
40 mg/m², intravenous infusion, administered once every 21 days (D1), for 3-4 cycles.
100 mg/m², intravenous infusion, administered once every 21 days (D1), for 3-4 cycles.
40 mg/m², oral, twice daily (BID), D1-14, every 21 days per cycle, for 3-4 cycles.
Subjects who complete 3-4 cycles of neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy.
The specific interval between neoadjuvant therapy and surgery will be determined by the investigator based on actual clinical circumstances.
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O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Pathological Complete Response Rate (pCR Rate)
Prazo: Perioperative, upon postoperative pathological evaluation
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Defined as the proportion of patients with no residual tumor cells in the resected tumor tissue and regional lymph nodes upon pathological evaluation.
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Perioperative, upon postoperative pathological evaluation
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Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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R0 Resection Rate
Prazo: Perioperative, upon postoperative pathological evaluation
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The proportion of patients with microscopically margin-negative resection, with no residual tumor cells either macroscopically or microscopically, and complete resection of the lesion.
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Perioperative, upon postoperative pathological evaluation
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Major Pathological Response Rate (MPR Rate)
Prazo: Perioperative, upon postoperative pathological evaluation
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Defined as the proportion of patients with ≤10% residual viable tumor cells in the postoperative pathological specimen.
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Perioperative, upon postoperative pathological evaluation
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Objective Response Rate (ORR)
Prazo: On Day 1 of every 2 cycles (each cycle is 21 days), prior to surgery
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The proportion of patients achieving complete response (CR) or partial response (PR) as assessed by RECIST version 1.1 criteria.
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On Day 1 of every 2 cycles (each cycle is 21 days), prior to surgery
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Disease Control Rate (DCR)
Prazo: On Day 1 of every 2 cycles (each cycle is 21 days), prior to surgery
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The proportion of patients achieving CR, PR, or stable disease (SD) among evaluable patients as assessed by RECIST version 1.1 criteria.
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On Day 1 of every 2 cycles (each cycle is 21 days), prior to surgery
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Number of Participants with Adverse Events (AEs) and Severity Graded
Prazo: From signing of ICF through 30 days after the last dose
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Defined as all adverse events occurring from enrollment (i.e., signing of the informed consent form) through 30 days after the last dose.
AEs will be coded using the MedDRA dictionary, with System Organ Class (SOC) and Preferred Term assigned to each adverse event.
The severity of adverse events will be graded according to NCI CTCAE version 5.0.
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From signing of ICF through 30 days after the last dose
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3-Year Disease-Free Survival Rate (DFS Rate)
Prazo: 3 years after treatment
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Defined as the proportion of patients without recurrence or metastasis within 3 years after treatment.
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3 years after treatment
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Outras medidas de resultado
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Peripheral blood ctDNA Biomarker
Prazo: Baseline and on Day 1 of every 2 cycles (each cycle is 21 days, synchronized with imaging evaluation), until prior to surgery
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Serial peripheral blood samples are collected at baseline and during neoadjuvant treatment.
Circulating tumor DNA (ctDNA) molecular profiles are detected by next-generation sequencing.
The exploratory analysis aims to evaluate the correlation between dynamic ctDNA alterations and treatment efficacy and safety outcomes.
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Baseline and on Day 1 of every 2 cycles (each cycle is 21 days, synchronized with imaging evaluation), until prior to surgery
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Peripheral blood multi-omics biomarker levels
Prazo: Baseline and on Day 1 of every 2 cycles (each cycle is 21 days, synchronized with imaging evaluation), until prior to surgery
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Serial peripheral blood samples are collected at baseline and during neoadjuvant treatment.
Genomic, transcriptomic, and proteomic multi-omics profiles in peripheral blood are detected using a multi-omics sequencing platform.
Exploratory analyses are performed to explore the association between peripheral blood multi-omics molecular features and treatment efficacy and safety.
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Baseline and on Day 1 of every 2 cycles (each cycle is 21 days, synchronized with imaging evaluation), until prior to surgery
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Tumor tissue multi-omics and tumor microenvironment immune signatures
Prazo: Baseline (pre-treatment biopsy) and perioperative (immediately after radical gastrectomy)
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Tumor specimens including fresh tissues and formalin-fixed paraffin-embedded (FFPE) sections are collected at baseline (pre-treatment biopsy) and immediately after radical gastrectomy.
Baseline and post-operative tumor tissues are subjected to genomic, transcriptomic, and proteomic multi-omics sequencing to characterize tumor biomarkers and tumor microenvironment immune molecular features.
All tissue collections do not interfere with routine clinical pathological diagnosis, and are performed with written informed consent.
Exploratory analyses will investigate the associations between tissue molecular signatures and treatment efficacy and safety outcomes.
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Baseline (pre-treatment biopsy) and perioperative (immediately after radical gastrectomy)
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Início do estudo
Conclusão Primária (Estimado)
Conclusão Primária
Conclusão do estudo (Estimado)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Produtos químicos orgânicos
- Procedimentos cirúrgicos, operatórios
- Hidrocarbonetos
- Cicloparaffinas
- Hidrocarbonetos, aliciclicos
- Hidrocarbonetos, cíclicos
- Terpenos
- Complexos de coordenação
- Taxóides
- Ciclodecanos
- Diterpenos
- Procedimentos cirúrgicos do sistema digestivo
- Docetaxel
- Oxaliplatina
- Gastrectomia
- tegafur-gimeracil-oteracil
Outros números de identificação do estudo
Outros números de identificação do estudo
- HN-QL1706-G/GEJ-002
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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