Phase II Basket Trial: Zanidatamab Plus Tislelizumab in HER2-Positive GI Tumors (UNION-HER2-BASKET)

NCT07243938 | Not Yet Recruiting Phase 2

• 1 other identifier: UNION-HER2-BASKET
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a prospective, multi-cohort clinical trial designed to evaluate the preliminary efficacy and safety of zanidatamab in combination with tislelizumab and chemotherapy/radiotherapy for patients with HER2-positive locally advanced or metastatic gastrointestinal tumors.

Conditions

Locally Advanced Rectal Cancer (LARC); Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma; Metastatic Colorectal Cancer (mCRC); Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (3)

• Complete Response Rate (CR Rate)

  The CR rate is defined as the sum of the pathological complete response rate (pCR rate) and the clinical complete response rate (cCR rate). To evaluate the preliminary efficacy of Zanidatamab in combination with Tislelizumab and chemoradiotherapy in neoadjuvant and organ-preserving treatment for patients with HER2-Positive locally advanced rectal cancer.

  cCR rate should be assessed every 6-9 weeks following treatment initiation until completion of the 18 weeks therapy; pCR assessment in non-cCR patients following surgery (within 20 weeks after treatment initiation).

• Pathological Complete Response Rate (pCR Rate)

  Following completion of 9 weeks of neoadjuvant therapy, an assessment will be conducted after radical surgical treatment.

  Within 15 weeks

• Progression-Free Survival (PFS)

  The time interval from the start of the first treatment (date of administration of zenidatumab or tislelizumab) to the date of the subject's first progression (PD) as assessed by the investigator using RECIST version 1.1

  Within 2 years

Secondary Outcomes (2)

• Adverse events (AEs) were graded according to the NCI CTCAE version 5·0

  an expected average of 2 years

• 3-year disease-Free Survival

  an expected average of 3 years

Study Arms (3)

Locally Advanced Rectal Cancer Cohort

EXPERIMENTAL

All patients receive short-course radiotherapy (SCRT) (dose: 25 Gy, 5 Gy × 5 fractions), followed sequentially by 6 cycles of CAPOX chemotherapy combined with zanidatamab and tislelizumab. Following completion of the above treatment, patients underwent clinical complete response (cCR) assessment. Those assessed as cCR were placed on watchful waiting, while those assessed as non-cCR underwent Total Mesorectal Excision (TME). Postoperatively, investigators selected treatment regimens based on patient status.

Radiation: short-course radiotherapy; Drug: Zanidatamab; Drug: Tisleizumab(BGB-A317); Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery

Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort

EXPERIMENTAL

Subjects receive 3 cycles of zanidatamab and tislelizumab combined with SOX therapy. Following treatment completion, undergo D2 gastrectomy. Postoperatively, continue with 5 cycles of zanidatamab and tislelizumab combined with SOX adjuvant therapy.

Drug: Zanidatamab; Drug: Tisleizumab(BGB-A317); Drug: Oxaliplatin; Drug: S-1; Procedure: D2

Advanced colorectal cancer cohort

EXPERIMENTAL

Subjects receive zanidatamab until disease progression or intolerable toxicity. Under specific circumstances, subjects may continue treatment after radiographic progression if the investigator assesses ongoing benefit; this decision will be made at the investigator's discretion.

Drug: Zanidatamab

Interventions

short-course radiotherapy RADIATION

25Gy, 5Gy×5

Locally Advanced Rectal Cancer Cohort

Zanidatamab DRUG

1800mg(\<70kg)/2400mg(≥70kg), IV，D1，Q3W

Advanced colorectal cancer cohort; Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort; Locally Advanced Rectal Cancer Cohort

Tisleizumab(BGB-A317) DRUG

200 mg，IV，D1，Q3W

Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort; Locally Advanced Rectal Cancer Cohort

Capecitabine DRUG

1000mg/m2/time，BID，PO，D1-14, Q3W

Locally Advanced Rectal Cancer Cohort

Oxaliplatin DRUG

130 mg/m2/次，IV，D1, Q3W

Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort; Locally Advanced Rectal Cancer Cohort

TME surgery PROCEDURE

The surgery was performed 4 - 6 weeks after the end of neoadjuvant therapy in patients who assessed as non-cCR.

Locally Advanced Rectal Cancer Cohort

S-1 DRUG

40\~60mg bid，po, d1\~14，Q3W （S-1：BSA \<1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2,50mg bid, BSA\>1.5m2, 60mg bid）

Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort

D2 PROCEDURE

Radical gastrectomy with D2 lymph node dissection was performed within 4-6 weeks after the completion of neoadjuvant therapy in patients without tumor progression on preoperative imaging assessment.

Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of gastric cancer and colorectal cancer
• Aged 18 to 75 years:
• Able to sign a written informed consent form and understand and comply with the requirements and evaluation schedule of this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• HER2-Positive: Immunohistochemistry (IHC) 3+ or IHC 2+ with FISH+ or NGS testing for high expression
• Locally advanced rectal cancer cohort:
• Histopathologically confirmed rectal adenocarcinoma
• Tumor tissue confirmed by immunohistochemistry (IHC) as pMMR (high expression of MLH1, MSH2, MSH6, and PMS2 proteins), or confirmed by PCR or NGS as MSI-L or MSS
• Tumor lower margin ≤10 cm from anal margin confirmed by colonoscopy, digital rectal examination, or MRI
• Clinical stage cT3-4N0M0/cTanyN+M0 (TNM staging per UICC/AJCC 8th edition; T and N stages assessed by MRI)
• Patients with one or more risk factors identified by MRI assessment: T4, tumor involvement of the mesorectal fascia (high MRF expression), extramural vascular invasion (high EMVI expression), ≥4 regional lymph node metastases (cN2), high lateral lymph node expression, or tumor margin ≤5 cm from the anal verge with strong organ preservation intent
• No prior antitumor therapy for rectal cancer (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.; excludes traditional Chinese medicine/formulated Chinese medicine treatment)
• Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort:
• Histopathologically confirmed adenocarcinoma of the stomach or gastroesophageal junction
• Clinical stage III-IVa (i.e., TNM staging T3\~4aN+M0 or T4bNanyM0, refer to UICC/AJCC 8th edition)

You may not qualify if:

• History of or concurrent other malignancies, except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or carcinoma in situ, provided complete remission was achieved at least 5 years prior to screening and no additional treatment is required or anticipated during the study period.
• Any of the following cardiovascular criteria:
• Cardiac chest pain occurring ≤28 days prior to the first study drug administration, defined as moderate pain limiting daily activities or exercise
• Symptomatic pulmonary embolism within ≤28 days prior to the first dose of study drug
• History of any acute myocardial infarction within ≤6 months prior to the first dose of study drug
• History of any New York Heart Association (NYHA) Class III or IV heart failure within ≤6 months prior to the first dose of study drug
• Any ventricular arrhythmia event of severity ≥ Grade 2 within ≤ 6 months prior to the first dose of the study drug
• History of any cerebrovascular accident within ≤6 months prior to the first dose of the study drug
• Corrected QT interval (QTc) (corrected using Fridericia's formula) ≥ 470 msec in females or ≥ 450 msec in males
• i) Note: If any patient's initial ECG shows a QTc interval \> 450 msec (male) or \> 470 msec (female), a follow-up ECG will be performed to verify the result h) Left ventricular ejection fraction (LVEF) ≤50% as assessed by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO). Follow-up assessment must use the same modality as the baseline assessment
• Any syncope or seizure occurring ≤28 days prior to the first study drug administration.
• Active autoimmune disease requiring systemic treatment within the past 2 years.
• Known history of human immunodeficiency virus (HIV) infection
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \> 500 IU/mL) or active HCV carriers with detectable HCV RNA; Note: Inactive hepatitis B surface antigen (HBsAg) carriers and treated, stable hepatitis B patients (HBV DNA \< 500 IU/mL) are eligible for enrollment
• History of interstitial lung disease, non-infectious pneumonia, or uncontrolled pulmonary conditions, including pulmonary fibrosis, acute pulmonary disease, etc.

Sponsors & Collaborators

• Tao Zhang: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

zanidatamab; Capecitabine; Oxaliplatin; S 1 (combination)

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Tao Zhang, Ph.D.

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Lin, Ph.D.

CONTACT

027-85871982; whxhlzy@hust.edu.cn

Tao Zhang, Ph.D.

CONTACT

taozhangxh@hust.edu.cn

Study Design

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

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 24, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share