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Gastric or Gastroesophageal Junction AdenocarcinomaPhase 2NCT07091227

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

A Phase 2 study testing AK112+oxaliplatin+capecitabine and oxaliplatin+capecitabine in people with Gastric or Gastroesophageal Junction Adenocarcinoma, run by Peking Union Medical College Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
AK112+oxaliplatin+capecitabine and oxaliplatin+capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteChina
Study dates
20 Jul 2025to 20 Jul 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 11) 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).
  • 12) Subjects (regardless of sex) with reproductive potential must agree to use highly effective contraception (failure rate <1%) from the start of study treatment to 120 days after last study dose (or 180 days if receiving chemotherapy).
  • 13) Breastfeeding is not permitted during the study period.

Who cannot join

  • 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.
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  • 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).
  • Active hepatitis C (HCV antibody positive with detectable HCV RNA).
  • Receipt of live vaccines within 30 days prior to first dose. Inactivated influenza vaccines are permitted; live attenuated intranasal influenza vaccine is not.
  • Pregnant or breastfeeding women.
  • Serious or uncontrolled systemic illnesses, including:
  • Significant arrhythmias or heart block
  • History of myocarditis, cardiomyopathy, MI, unstable angina, CHF within 12 months
  • Gastrointestinal conditions (e.g., active ulcers, varices, perforation, abscess) within 6 months
  • Recent COPD exacerbation (within 1 month)
  • Grade ≥3 thromboembolic events or cerebrovascular accidents within 6 months
  • Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite treatment)
  • Non-infectious pneumonitis or interstitial lung disease
  • Pulmonary tuberculosis
  • Active systemic infection
  • Decompensated liver disease
  • Poorly controlled diabetes (FBG >10 mmol/L or random BG >16 mmol/L)
  • Proteinuria ≥ ++ or 24-hour urine protein > 1.0 g
  • Psychiatric illness interfering with compliance or safety.
  • Major surgery or significant trauma within 30 days prior to first dose, or planned major surgery within 30 days post first dose (except minor procedures).
  • Tumor necrosis on imaging, deemed high risk for bleeding by investigator.
  • History of severe bleeding or coagulation disorders; active bleeding within 1 month (e.g., hematemesis, hemoptysis, significant epistaxis); long-term anticoagulation for atrial fibrillation with CHADS2 ≥ 2.
  • Any condition or laboratory abnormality that, in the opinion of the investigator, may interfere with the study results or subject safety.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Xiaoyan Chen contact

86+18811725929

yan_pumch@126.com

China1 site

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

    Beijing, 100730

Other trials in China

About this study

Official title: Efficacy and Safety of AK112 Combined Chemotherapy as Neoadjuvant Treatment for Signet Ring Cell-containing Gastric or Gastroesophageal Junction Adenocarcinoma

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.

Read more

Key Research Questions

  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. What are the safety profile and additional efficacy outcomes of AK112 combined with chemotherapy in this patient population?

To answer these questions, the study will compare the combination of AK112 and chemotherapy with chemotherapy alone.

Participant Procedures

Eligible participants will:

  1. Receive standard-dose AK112 in combination with chemotherapy every 3 weeks for a total of 4 cycles prior to surgery.
  2. 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.
  3. 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).
  4. Postoperatively, adjuvant therapy will be administered at the investigator's discretion. Patients will be followed until disease recurrence or metastasis.
  5. Attend clinic visits every 6 weeks during the neoadjuvant phase for evaluations and laboratory tests.
  6. Maintain a symptom diary throughout the study period.
  7. 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.

Optional Imaging Substudy FAPI-PET/CT imaging will be explored as an optional diagnostic modality. Participation in this substudy will require separate informed consent and will be conducted under a future protocol amendment (pending IRB approval).

Being tested
AK112+oxaliplatin+capecitabine, oxaliplatin+capecitabine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AK112+oxaliplatin+capecitabineDrug

    Also called AK112+XELOX

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

  • oxaliplatin+capecitabineDrug

    Also called XELOX

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

Study groups in NCT07091227
Study groupRoleWhat they receive
AK112+XELOXExperimentalThe participants received neoadjuvant therapy with AK112+oxaliplatin+capecitabine
Receives: Drug: AK112+oxaliplatin+capecitabine
XELOXActive comparatorThe participants received neoadjuvant therapy with oxaliplatin+capecitabine
Receives: Drug: oxaliplatin+capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Complete Response (pCR)

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

    Measured: At surgery

Secondary outcomes (5)

  1. Objective Response Rate，ORR

    Proportion of participants achieving CR or PR per RECIST v1.1 assessed via contrast-enhanced CT/MRI

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

  2. Disease-Free Survival, DFS

    The time between postoperative and disease recurrence or (for any reason) death.

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

  3. Treatment-Emergent Adverse Events (TEAEs)

    Incidence of adverse events graded by CTCAE v6.0

    Measured: First dose to 90 days post-surgery

  4. Serious Adverse Events (SAE)

    Serious AEs leading to discontinuation

    Measured: First dose to 90 days post-surgery

  5. R0 Resection Rate

    Percentage of participants achieving microscopically margin-negative resection

    Measured: At surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2025
  2. Study start20 Jul 2025 (estimated)
  3. Primary completion20 Jul 2026 (estimated)
  4. Study completion20 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07091227
Sponsor's protocol ID
K7937
Status last verified
May 2025
First submitted
2 Jul 2025
Last updated
29 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) underlying published results (including baseline characteristics, outcome measures, and protocol deviations) will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AK112+oxaliplatin+capecitabine and oxaliplatin+capecitabine in people with Gastric or Gastroesophageal Junction Adenocarcinoma, run by Peking Union Medical College Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xiaoyan Chen (86+18811725929, yan_pumch@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (pCR) (time frame: At surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07091227.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.

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