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
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Zápis (Odhadovaný)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
Studijní kontakt
- Jméno: Yongxu Jia
- Telefonní číslo: 66271157
- E-mail: jiayongxu111@126.com
Studijní místa
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Henan
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Zhengzhou, Henan, Čína, 450000
- The First Affiliated Hospital of Zhengzhou University
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Kontakt:
- Yongxu Jia
- Telefonní číslo: 66271157
- E-mail: jiayongxu111@126.com
-
-
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: 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.
Ostatní jména:
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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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Pathological Complete Response Rate (pCR Rate)
Časové okno: 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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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
R0 Resection Rate
Časové okno: Perioperative, upon postoperative pathological evaluation
|
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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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)
Časové okno: 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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Další výstupní opatření
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Peripheral blood ctDNA Biomarker
Časové okno: 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
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Spolupracovníci
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- HN-QL1706-G/GEJ-002
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Plánujete sdílet data jednotlivých účastníků (IPD)?
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Studuje produkt zařízení regulovaný americkým úřadem FDA
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