Phase II Clinical Study of Adebrelimab Plus Apatinib and SOX Regimen for Conversion Therapy of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Beijing Friendship Hospital
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- R0 resection rate
Study Overview
Brief Summary
This is a prospective, single-center, single-arm, open phase II clinical study. Forty-nine participants with pathologically or cytologically confirmed gastric cancer or gastroesophageal junction cancer are scheduled to be enrolled in this study. All participants will be treated with 2 to 8 cycles of adebrelimab, apatinib, oxaliplatin, and tigio before surgery. Participants will evaluate the treatment effect after every 2 cycles of medication. By the investigator assessment as an operable subject, apatinib was discontinued for one cycle. The adjuvant treatment will be determined by the investigators based on the participants' postoperative pathology results. Participants requiring adjuvant therapy, with a postoperative interval of at least 4 weeks, but not more than 10 weeks. When the resection standard isn't met for 8 cycles of treatment, the treatment is switched to a maintenance phase, which the subject treatment regimen is determined by the investigator. During the treatment period, participants will receive the study drugs on Day 1 of each 21-day cycle until evidence of disease progression or unacceptable toxicity.
Detailed Description
Study Design: This is a prospective, single-center, single-arm, open-label Phase II clinical study. The study aims to evaluate the efficacy and safety of Adebrelimab combined with Apatinib and SOX regimen as conversion therapy for patients with advanced, unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. The study plans to enroll approximately 49 participants who are assessed by investigators as having conversion therapy potential (defined as single organ metastasis, retroperitoneal lymph node metastasis, supraclavicular lymph node metastasis, limited peritoneal metastasis, or invasion of surrounding organs).
Treatment Protocol: Eligible participants will receive a four-drug combination therapy consisting of Adebrelimab, Apatinib Mesylate, Oxaliplatin, and S-1. The treatment is administered in 3-week cycles:
Adebrelimab: 1200 mg, intravenous infusion on Day 1.
Apatinib Mesylate: 250 mg, oral, once daily.
Oxaliplatin: 130 mg/m², intravenous infusion on Day 1.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-75 years at the time of enrollment, with an estimated life expectancy of ≥ 3 months.
- •Histologically or cytologically confirmed gastric cancer or gastroesophageal junction cancer, predominantly adenocarcinoma.
- •Unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma (Stage III or IV), as determined by the investigator based on CT, MRI, and/or PET-CT.
- •Disease with conversion (translational) therapeutic potential, as assessed by the investigator.
- •No prior anti-tumor treatment, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other systemic anticancer therapies.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Adequate hematologic function within 14 days prior to enrollment:
- •White blood cell count ≥ 3.5 × 10⁹/L.
- •Absolute neutrophil count ≥ 1.5 × 10⁹/L.
- •Hemoglobin ≥ 90 g/L (9.0 g/dL).
- •Platelet count ≥ 100 × 10⁹/L.
- •Adequate hepatic function within 14 days prior to enrollment:Total bilirubin ≤ 1.5 × upper limit of normal (ULN);ALT and AST ≤ 2.5 × ULN in patients without liver metastases;ALT and AST ≤ 5 × ULN in patients with liver metastases;Adequate renal function:Serum creatinine ≤ 1.5 × ULN;Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and agree to use effective contraception during the study and for at least 12 weeks after the last dose.
- •Male participants must be surgically sterile or agree to use effective contraception during the study and for at least 12 weeks after the last dose
- •Ability to understand and willingness to sign a written informed consent form
- •Expected to comply with study procedures and follow-up requirements
Exclusion Criteria
- •HER2-positive gastric or gastroesophageal junction adenocarcinoma.
- •Conditions that may significantly affect oral drug absorption, including inability to swallow, persistent nausea or vomiting, chronic diarrhea, or intestinal obstruction.
- •Known hypersensitivity or allergy to adebrelimab, apatinib, oxaliplatin, S-1 (tegafur/gimeracil/oteracil), or any of their excipients.
- •History of severe allergic reactions to monoclonal antibodies.
- •Active autoimmune disease or autoimmune disorders requiring systemic treatment.
- •Congenital or acquired immunodeficiency.
- •Use of systemic immunosuppressive therapy within 14 days prior to the first dose of study treatment.
- •Administration of live attenuated vaccines within 4 weeks prior to the first dose or planned during the study period.
- •Severe infection within 4 weeks prior to initiation of study treatment.
- •History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- •Evidence of interstitial lung disease, including pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or severely impaired pulmonary function.
- •Uncontrolled hypertension despite at least 3 months of antihypertensive treatment.
- •Uncontrolled clinically significant cardiovascular disease.
- •High risk of severe bleeding, as judged by the investigator.
- •Peripheral neuropathy of Grade > 2 according to CTCAE.
- •Participation in another interventional clinical trial within 4 weeks prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
- •Any condition that, in the investigator's judgment, makes the participant unsuitable for study participation.
Arms & Interventions
Adebrelimab + Apatinib + SOX
Participants receive Adebrelimab, Apatinib, Oxaliplatin, and S-1 as conversion therapy. Treatment is administered in 3-week cycles for 2-8 cycles, followed by surgical assessment.
Intervention: Apatinib (Drug)
Adebrelimab + Apatinib + SOX
Participants receive Adebrelimab, Apatinib, Oxaliplatin, and S-1 as conversion therapy. Treatment is administered in 3-week cycles for 2-8 cycles, followed by surgical assessment.
Intervention: SOX Chemotherapy (Drug)
Adebrelimab + Apatinib + SOX
Participants receive Adebrelimab, Apatinib, Oxaliplatin, and S-1 as conversion therapy. Treatment is administered in 3-week cycles for 2-8 cycles, followed by surgical assessment.
Intervention: Adebrelimab (Drug)
Outcomes
Primary Outcomes
R0 resection rate
Time Frame: At the time of definitive surgery following completion of neoadjuvant treatment (within 6 months from enrollment)
Proportion of participants who achieve R0 resection, defined as microscopically margin-negative resection confirmed by postoperative pathological examination.
Adverse Events (AE)
Time Frame: From treatment initiation to 30 days after the last dose of study treatment (up to approximately 6 months).
Incidence, nature, and severity of treatment-emergent adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Secondary Outcomes
- Objective response rate (ORR)(up to 1year)
- Overall survival (OS)(Up to 3 years)
- Disease Free Survival (PFS)(Up to 2 years)
Investigators
Deng Wei
Chief Physician
Beijing Friendship Hospital