Perioperative Ivonescimab Plus S-1 and Oxaliplatin (SOX) for Locally Advanced Gastric or GEJ Adenocarcinoma

Official title

Perioperative Ivonescimab Plus S-1 and Oxaliplatin (SOX) Versus SOX Alone for Locally Advanced Gastric or GEJ Adenocarcinoma: A Multicenter Randomized Phase II Study

Overview

The purpose of this clinical trial is to evaluate whether perioperative ivonescimab in combination with S-1 and oxaliplatin (SOX) is effective in treating locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. The study will also assess the safety profile of this treatment regimen. Primary Objective: To determine whether perioperative ivonescimab plus SOX improves the pathological complete response (pCR) rate compared with SOX alone in patients with locally advanced gastric or GEJ adenocarcinoma. Study Design: Participants will be randomly assigned to receive either ivonescimab plus SOX or SOX alone to evaluate the potential added benefit of ivonescimab in this setting. Participation Details: Participants will receive the assigned treatment (ivonescimab plus SOX or SOX alone) every 21 days for approximately 4 months. They will visit the clinic once every 3 weeks for evaluations, laboratory tests, and monitoring. Participants will be asked to keep a daily diary to record any symptoms or side effects experienced during the study.

Detailed description

To evaluate the efficacy and safety of ivonescimab in combination with S-1 and oxaliplatin (SOX) for the treatment of locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant (perioperative) setting, with the goal of improving the pathological complete response (pCR) rate.

Interventions

• Drug Ivonescimab (20mg/kg Q3W)
  ivonescimab (20 mg/kg), four 3-week cycles were administered; ivonescimab was not administered in cycle 4. .
• Drug Oxaliplatin
  Oxaliplatin (130 mg/m², administered intravenously on day 1), four 3-week cycles were administered.
• Drug S-1
  S-1 (administered orally twice daily on days 1-14 of each 21-day cycle, with the daily dose determined by body surface area: \<1.25 m², 80 mg/day; ≥1.25 to \<1.5 m², 100 mg/day; ≥1.5 m², 120 mg/day), four 3-week cycles were administered.

Primary outcome measures

• Total pathological complete response (pCR; ypT0) assessed by investigators, defined as the complete absence of tumor cells in the primary tumor on pathological examination. [Time frame: Perioperative]

Secondary outcome measures (9)

• Event-free survival (EFS) [Time frame: Through study completion,an average of 2 years]
• major pathologic response [Time frame: Perioperative]
• R0 resection [Time frame: Perioperative]
• overall survival (OS) [Time frame: Through study completion,an average of 2 years]
• disease-free survival (DFS) [Time frame: Through study completion,an average of 2 years]
• safety [Time frame: Through study completion,an average of 2 years]
• surgery-related complications [Time frame: Through study completion,an average of 2 years]
• An exploratory endpoint [Time frame: Through study completion,an average of 2 years]
• Quality of life [Time frame: Perioperative]

Eligibility criteria

Inclusion criteria

• Age 18-75 years.
• Histologically confirmed gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Clinically staged as T3-4a N+ M0 by computed tomography (CT) or magnetic resonance imaging (MRI).
• Considered eligible for curative resection.
• No prior antitumor therapy for the current disease.
• Adequate organ function, including hepatic, renal, and bone marrow function, as per prespecified laboratory criteria.
• Expected survival of ≥6 months.

Exclusion criteria

• Known mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumor.
• Uncontrolled hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥ 90 mmHg despite optimized antihypertensive therapy, or hypertension complicated by acute events (e.g., hypertensive crisis, hypertensive encephalopathy) that cannot be stably controlled.
• Tumor lesions with a bleeding tendency, including but not limited to: active ulcerative tumor lesions, hematemesis within 2 months prior to informed consent, high risk of major gastrointestinal bleeding as determined by the investigator.
• History of thromboembolic or arterial/venous vascular events within 6 months prior to enrollment, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism.
• Gastrointestinal perforation or gastrointestinal obstruction within 6 months prior to enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• West China Hospital, Sichuan University — Chengdu

Publications

• Andre T, Tougeron D, Piessen G, de la Fouchardiere C, Louvet C, Adenis A, Jary M, Tournigand C, Aparicio T, Desrame J, Lievre A, Garcia-Larnicol ML, Pudlarz T, Cohen R, Memmi S, Vernerey D, Henriques J, Lefevre JH, Svrcek M. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenoca PMID 35969830
• Lorenzen S, Gotze TO, Thuss-Patience P, Biebl M, Homann N, Schenk M, Lindig U, Heuer V, Kretzschmar A, Goekkurt E, Haag GM, Riera-Knorrenschild J, Bolling C, Hofheinz RD, Zhan T, Angermeier S, Ettrich TJ, Siebenhuener AR, Elshafei M, Bechstein WO, Gaiser T, Loose M, Sookthai D, Kopp C, Pauligk C, Al-Batran SE; AIO and SAKK Study Working Groups. Perioperative Atezolizumab Plus Fluorouracil, Leucovo PMID 37963317
• Shah MA, Kennedy EB, Alarcon-Rozas AE, Alcindor T, Bartley AN, Malowany AB, Bhadkamkar NA, Deighton DC, Janjigian Y, Karippot A, Khan U, King DA, Klute K, Lacy J, Lee JJ, Mehta R, Mukherjee S, Nagarajan A, Park H, Saeed A, Semrad TJ, Shitara K, Smyth E, Uboha NV, Vincelli M, Wainberg Z, Rajdev L. Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline. J Clin Oncol. PMID 36603169
• Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, Bang YJ, De Vita F, Landers G, Yen CJ, Chau I, Elme A, Lee J, Ozguroglu M, Catenacci D, Yoon HH, Chen E, Adelberg D, Shih CS, Shah S, Bhagia P, Wainberg ZA. Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061 PMID 33792646
• Nie RC, Chen GM, Yuan SQ, Kim JW, Zhou J, Nie M, Feng CY, Chen YB, Chen S, Zhou ZW, Wang Y, Li YF. Adjuvant Chemotherapy for Gastric Cancer Patients with Mismatch Repair Deficiency or Microsatellite Instability: Systematic Review and Meta-Analysis. Ann Surg Oncol. 2022 Apr;29(4):2324-2331. doi: 10.1245/s10434-021-11050-6. Epub 2021 Nov 18. PMID 34796431
• Choi YY, Bae JM, An JY, Kwon IG, Cho I, Shin HB, Eiji T, Aburahmah M, Kim HI, Cheong JH, Hyung WJ, Noh SH. Is microsatellite instability a prognostic marker in gastric cancer? A systematic review with meta-analysis. J Surg Oncol. 2014 Aug;110(2):129-35. doi: 10.1002/jso.23618. Epub 2014 Apr 15. PMID 24737677
• Pietrantonio F, Miceli R, Raimondi A, Kim YW, Kang WK, Langley RE, Choi YY, Kim KM, Nankivell MG, Morano F, Wotherspoon A, Valeri N, Kook MC, An JY, Grabsch HI, Fuca G, Noh SH, Sohn TS, Kim S, Di Bartolomeo M, Cunningham D, Lee J, Cheong JH, Smyth EC. Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer. J Clin Oncol. 2019 Dec 10;37(35): PMID 31513484
• Tran-Minh ML, Lehmann-Che J, Lambert J, Theou-Anton N, Pote N, Dior M, Mary F, Goujon G, Gardair C, Schischmanoff O, Kaci R, Cucherousset N, Bertheau P, Couvelard A, Aparicio T; for NORDICAP. Prevalence and prognosis of microsatellite instability in oesogastric adenocarcinoma, NORDICAP 16-01. Clin Res Hepatol Gastroenterol. 2021 Jul;45(4):101691. doi: 10.1016/j.clinre.2021.101691. Epub 2021 Apr 20 PMID 33852952

Identifiers

NCT: NCT07374250 · Huaxi gastric cancer · Huaxi

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗