Multi-omics Sequencing in Neoadjuvant Immunotherapy of Gastrointestinal Tumors

NCT05515796 | Completed Phase 2 DMC

• 1 other identifier: DP-GE-ICI
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 1

Brief Summary

immunotherapy，gastric cancer，rectal cancer，biomark

Conditions

Immunotherapy; Gastric Cancer; Rectal Cancer; Radiotherapy; Chemotherapy Effect

Keywords

Immunotherapy; Gastric Cancer; Rectal Cancer; neoadjuvant; Terelizumab (aka Tislelizumab); radiotherapy; oxaliplatin; capecitabine

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging

  6 months

Secondary Outcomes (4)

• Major pathologic response (MPR)

  6 months

• Overall survival (OS)

  2 years

• Disease-free survival (DFS)

  2 years

• R0 resection rate

  6 months

Other Outcomes (5)

• Correlation analysis of evaluating the relationship between clinicopathological characteristics and neoadjuvant immunochemotherapy efficacy

  2 years

• Correlation analysis of evaluating the relationship between multi-omics analysis of tumor tissue and neoadjuvant immunochemotherapy efficacy

  2 years

• EORTC QLQ-C30(V3)

  2 years

Study Arms (3)

Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative)

EXPERIMENTAL

CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative): Cycle 1 up to Cycle 3 CapeOX + Terelizumab (aka Tislelizumab) therapy Cycle: Day 1 through Day 21

Drug: Terelizumab (aka Tislelizumab); Drug: CapeOx

Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )

EXPERIMENTAL

CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive ): Cycle 1 up to Cycle 3 CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) Cycle: Day 1 through Day 21

Drug: Terelizumab (aka Tislelizumab); Drug: CapeOx; Drug: Trastuzumab

Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)

EXPERIMENTAL

Rectal cancer: Cycle 1:25 Gy/5 fractions (Day 1 through Day 7) Cycle 2 up to Cycle 3 CapeOX + Terelizumab (aka Tislelizumab) therapy(Day 1 through Day 21)

Drug: Terelizumab (aka Tislelizumab); Drug: CapeOx; Radiation: Radiotherapy

Interventions

Terelizumab (aka Tislelizumab) DRUG

q3w Terelizumab (aka Tislelizumab) 200mg on day 1 of each cycle

Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative); Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive ); Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)

CapeOx DRUG

Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine:Dose of 1000mg/m2,14days

Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative); Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive ); Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)

Trastuzumab DRUG

q3w Trastuzumab (6 mg/kg following an initial loading dose of 8 mg/kg) on day 1 of each cycle

Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )

Radiotherapy RADIATION

25 Gy/5 fractions

Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients are able to understand and voluntarily sign the written informed consent, which must be signed prior to the implementation of the designated research procedures required by the study.
• The age at the time of signing the informed consent form (ICF) is ≥ 18 years old, both male and female.
• Locally advanced or metastatic gastric / gastroesophageal junction adenocarcinoma (clinical stage ≥ T2N0M0) and pMMR/MSS(tumor biopsy immunohistochemical identified pMMR or next generation sequencing identified MSS) locally advanced rectal adenocarcinoma (clinical stage T3-4N0M0 or T1-4N+M0 ) were diagnosed by comprehensive evaluation.
• The patients are willing to provide fresh tissue for biomarker analysis, and the tissue samples provided are of sufficient quality to evaluate the status of biomarkers. If sufficient tissue is not provided, repeated sampling may be required.
• The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• The expected survival time was ≥ 3 months.
• The patient has adequate organs function
• The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1.5\*10\^9/L, hemoglobin ≥90g/L (5.58 mmol/L), and platelets ≥100\*10\^9/L.
• The patient has adequate renal function as defined by a serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥50 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).
• The patient has adequate hepatic function as defined by a total bilirubin ≤1.5 mg/dL (25.65 μmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases).
• The patient must have adequate coagulation function as defined by international normalized ratio (INR) ≤1.5
• Within 7 days before the first administration, women of childbearing age must confirm that the serum pregnancy test is negative and agree to use effective contraceptives during the study period and within 180 days after the last administration. In this program, women of childbearing age are defined as sexually mature women:
• No hysterectomy or bilateral ovariectomy
• Natural menopause does not last for 24 months (amenorrhea after cancer treatment does not rule out fertility) (that is, menstruation occurs at any time in the previous 24 months).
• For male patients whose sexual partners are women of childbearing age, they must agree to use effective contraception during the study drug use and within 180 days after the last administration.

You may not qualify if:

• Palliative local treatment was given to non-target lesions within 2 weeks before the first administration, and systemic non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc.) was received within 2 weeks before the first administration. Chinese herbal medicine or proprietary Chinese medicine with anti-tumor indications was received within 2 weeks before the first administration.
• The patient has previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy, etc. any treatment aimed at the immune mechanism of tumor.
• There was a history of gastrointestinal perforation and gastrointestinal fistula within 6 months before the first administration. If the perforation or fistula has been removed or repaired, and the disease has been judged by the researchers to recover or remission, it may be allowed to join the group.
• Active or previously recorded inflammatory bowel disease (such as Crohn's disease or ulcerative colitis). Unable to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect drug use and absorption.
• There were active malignant tumors in the past 3 years, except for tumors that participated in the study and local tumors that had been cured. such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast cancer in situ, localized prostate cancer and so on.
• Active or untreated brain metastases, meningeal metastases, spinal cord compression or leptomeningeal diseases are known.
• However, the patients who met the following requirements and had measurable lesions outside the central nervous system were allowed to enter the group: asymptomatic after treatment, imaging was stable for at least 4 weeks before the start of treatment (such as no new or enlarged brain metastases). And systemic corticosteroids and anticonvulsant drugs have been stopped for at least 2 weeks.
• There are pleural effusion with clinical symptoms, pericardial effusion or ascites requiring frequent drainage (≥ 1 / month).
• Study active autoimmune diseases that require systematic treatment within 2 years before the start of treatment, or researchers determine the existence of autoimmune diseases that may recur or plan treatment. Except for the following:
• Skin diseases that do not require systematic treatment (e.g. vitiligo, hair loss, psoriasis or eczema)
• Hypothyroidism caused by autoimmune thyroiditis requires only a stable dose of hormone replacement therapy.
• Type I diabetes mellitus requiring only a stable dose of insulin replacement therapy
• Asthma has been completely relieved in childhood and no intervention is needed in adults.
• The researchers determined that the disease would not recur without external triggers.
• There are any of the following cardio-cerebrovascular diseases or cardio-cerebrovascular risk factors:

Sponsors & Collaborators

• Daping Hospital and the Research Institute of Surgery of the Third Military Medical University: lead

Study Sites (1)

Army Medical Center

Chongqing, Other (Non U.s.), 400000, China

Location

MeSH Terms

Conditions

Stomach Neoplasms; Rectal Neoplasms

Interventions

Trastuzumab; Radiotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• wang bin

  Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Gastroenterology

Model Details: Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative)（n=80） Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )（n=20） Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)（n=100）

Study Record Dates

• First Submitted: August 20, 2022
• First Posted: August 25, 2022
• Study Start: September 1, 2022
• Primary Completion: March 25, 2026
• Study Completion: March 25, 2026
• Last Updated: April 1, 2026

Record last verified: 2025-08

Locations

CN (1)