Efficacy and Safety of AK112 Combined Chemotherapy as Neoadjuvant Treatment for Signet Ring Cell-containing G/GEJ Adenocarcinoma

NCT07091227 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: K7937
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Study Overview The primary objective of this clinical trial is to evaluate the efficacy and safety of AK112 in combination with chemotherapy as a neoadjuvant treatment for patients with locally advanced, resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma containing signet ring cells. Key Research Questions

1. 1.Does neoadjuvant treatment with AK112 plus chemotherapy improve the pathological complete response (pCR) rate compared to chemotherapy alone in patients with locally advanced G/GEJ adenocarcinoma with signet ring cells?
2. 2.What are the safety profile and additional efficacy outcomes of AK112 combined with chemotherapy in this patient population?
3. 3.Receive standard-dose AK112 in combination with chemotherapy every 3 weeks for a total of 4 cycles prior to surgery.
4. 4.Undergo preoperative CT or MRI imaging within 3-4 weeks after the last treatment cycle to assess tumor response and evaluate eligibility for curative resection.
5. 5.If no evidence of disease progression is observed and surgical evaluation is favorable, patients will undergo curative-intent gastrectomy within 6 weeks of completing neoadjuvant therapy (including oral agents, if any).
6. 6.Postoperatively, adjuvant therapy will be administered at the investigator's discretion. Patients will be followed until disease recurrence or metastasis.
7. 7.Attend clinic visits every 6 weeks during the neoadjuvant phase for evaluations and laboratory tests.
8. 8.Maintain a symptom diary throughout the study period.
9. 9.Undergo follow-up assessments every 3 months, starting from the first dose of study medication until 30 days after the last dose or the initiation of a new anti-tumor therapy.

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR)

  Absence of viable tumor cells in primary tumor and lymph nodes (Becker TRG 1a)

  At surgery

Secondary Outcomes (5)

• Objective Response Rate，ORR

  After 2 neoadjuvant cycles (6 weeks), and 4 neoadjuvant cycles(12 weeks)

• Disease-Free Survival, DFS

  Assessed every 12 weeks via CT/MRI up to 60 months from postoperative.

• Treatment-Emergent Adverse Events (TEAEs)

  First dose to 90 days post-surgery

• Serious Adverse Events (SAE)

  First dose to 90 days post-surgery

• R0 Resection Rate

  At surgery

Study Arms (2)

AK112+XELOX

EXPERIMENTAL

The participants received neoadjuvant therapy with AK112+oxaliplatin+capecitabine

Drug: AK112+oxaliplatin+capecitabine

XELOX

ACTIVE COMPARATOR

The participants received neoadjuvant therapy with oxaliplatin+capecitabine

Drug: oxaliplatin+capecitabine

Interventions

AK112+oxaliplatin+capecitabine DRUG

participants will receive standard dose treatment of AK112 combined with oxaliplatin+capecitabine every 3 weeks for 4 cycles before surgery.

Also known as: AK112+XELOX

AK112+XELOX

oxaliplatin+capecitabine DRUG

participants will receive standard dose treatment of oxaliplatin+capecitabine every 3 weeks for 4 cycles before surgery

Also known as: XELOX

XELOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must voluntarily agree to participate in the clinical trial and sign a written informed consent form (ICF) before undergoing any trial-related procedures.
• Male or female subjects aged ≥18 and ≤75 years at the time of signing the informed consent.
• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction with signet ring cell components. Diagnosis of locally advanced disease (based on AJCC 8th edition) must be made within 4 weeks prior to randomization.
• Tumor staging: cT3-4a or cN+ (M0) as determined by endoscopic ultrasound and/or contrast-enhanced CT/MRI. Diagnostic laparoscopy may be used as needed. The tumor must be assessed as resectable by the investigator.
• Immunohistochemical testing confirms proficient mismatch repair (pMMR) status and HER-2 negativity (IHC 0 or 1+, or IHC 2+ with negative FISH for HER-2 amplification).
• No prior systemic treatment for the current malignancy, including surgery, chemotherapy, radiotherapy, or immunotherapy.
• Eligible for radical surgery with no surgical contraindications as determined by a qualified surgeon.
• ECOG performance status of 0 or 1 within 7 days before randomization.
• Estimated life expectancy \> 6 months.
• Adequate organ function, as demonstrated by the following laboratory results (without blood product transfusion or cytokine support within 2 weeks prior to first dose):
• Hematologic: WBC ≥ 3.5 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, Platelets ≥ 100 × 10⁹/L, Hemoglobin ≥ 90 g/L Hepatic: Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN Renal: Serum creatinine ≤ 1.0 × ULN, Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula) Coagulation: INR, APTT, PT ≤ 1.5 × ULN Thyroid: TSH within normal limits. If TSH is abnormal, subjects with normal total T3 (or FT3) and FT4 may be enrolled.
• Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram; cardiac assessment may be required for patients with cardiac comorbidities.
• Hepatitis B serology: HBsAg (-) and anti-HBc (-). If HBsAg (+) or anti-HBc (+), HBV-DNA must be \<1000 copies/mL or \<200 IU/mL or below the site-specific ULN.
• HCV antibody (-). Subjects with positive HCV antibody but negative HCV-RNA may be considered eligible.
• \) For women of childbearing potential: Negative serum or urine pregnancy test within 7 days before randomization. If urine test is inconclusive, a serum test is required. Postmenopausal status is defined as ≥12 months of amenorrhea or surgical sterilization (bilateral oophorectomy/hysterectomy).

You may not qualify if:

• Histology other than adenocarcinoma with signet ring cell features, including squamous cell carcinoma, neuroendocrine carcinoma, or other subtypes.
• Tumor exhibiting deficient MMR (dMMR) or HER-2 positivity (IHC 3+, or IHC 2+ with FISH-confirmed HER-2 amplification).
• Unresectable tumors or subjects unwilling or unable to undergo surgery due to medical, anatomical, or personal reasons.
• History of other malignancies within 5 years prior to enrollment, excluding certain cured cancers (e.g., basal cell carcinoma, carcinoma in situ of cervix/breast/prostate/bladder).
• Evidence of active bleeding on endoscopy.
• Participation in another interventional clinical study or use of investigational drugs/devices within 4 weeks prior to enrollment.
• Prior immunotherapy including immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1, anti-CTLA-4, anti-TIGIT, etc.) or cellular immunotherapy.
• Use of traditional Chinese medicine with antitumor or immunomodulatory effects within 2 weeks prior to first dose.
• Active autoimmune disease requiring systemic therapy in the last 2 years. Hormonal replacement therapies are allowed.
• Use of systemic corticosteroids or immunosuppressants within 7 days before first dose (except ≤10 mg/day prednisone equivalent).
• Prior or planned organ/bone marrow transplantation (excluding corneal transplant).
• Known hypersensitivity to investigational products.
• Conditions affecting oral administration of capecitabine (e.g., dysphagia, intestinal obstruction).
• HIV infection (HIV-1/2 antibody positive).
• Active hepatitis B (HBsAg positive and HBV DNA \> ULN).

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Akeso Biopharma Co., Ltd.: collaborator

Study Sites (1)

Department of Cancer Medical Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College

Beijing, 100730, China

Location

MeSH Terms

Interventions

XELOX

Study Officials

• Yi Ba

  Department of Cancer Medical Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing，100730

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoyan Chen

CONTACT

86+18811725929; yan_pumch@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: July 29, 2025
• Study Start: July 20, 2025
• Primary Completion (Estimated): July 20, 2026
• Study Completion (Estimated): July 20, 2029
• Last Updated: July 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after primary publication and available for 10 years
• Access Criteria: 1. Researchers must submit a methodologically sound proposal to \[DataAccess@PUMCH.cn\](mailto:DataAccess@PUMCH.cn) 2. Approval by the sponsor's independent data access committee 3. Signed data sharing agreement 4. Proposals may be rejected for commercial/competitive reasons

Locations

CN (1)