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Locally Advanced Rectal Cancer (LARC)Phase 2NCT07243938

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

A Phase 2 study testing short-course radiotherapy, Zanidatamab and Tisleizumab(BGB-A317) in people with Locally Advanced Rectal Cancer (LARC) and Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma, run by Tao Zhang.

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
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
short-course radiotherapy, Zanidatamab and Tisleizumab(BGB-A317)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
No sites listed yet
Study dates
15 Jan 2026to 1 Jun 2031
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

  • 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:
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  • 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)
  • No prior antitumor therapy for gastric or gastroesophageal junction adenocarcinoma (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.; excludes traditional Chinese medicine/Chinese patent medicine treatment)
  • Advanced colorectal cancer cohort:
  • Histopathologically confirmed advanced colorectal cancer
  • Previous systemic anticancer therapy for metastatic colorectal cancer with documented failure, including fluoropyrimidine, oxaliplatin, irinotecan, cetuximab, or bevacizumab (excluding contraindications). Prior anti-HER2 therapy permitted
  • At least one measurable lesion defined according to RECIST 1.1
  • Expected survival > 3 months
  • Good organ function within ≤7 days prior to first study drug administration, as demonstrated by the following laboratory values:
  • No blood or platelet transfusions or growth factor support therapy within ≤14 days prior to blood sample collection during the screening period, and must meet:
  • ANC ≥ 1.5 x 10⁹/L
  • Platelet count ≥ 100 x 10⁹/L
  • Hemoglobin ≥ 90 g/L
  • Serum creatinine ≤ 1.5 times the upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver metastases)
  • Serum total bilirubin ≤ 1.5 times ULN (≤ 3 times ULN for patients with liver metastases)
  • International Normalized Ratio (INR) ≤ 1.5 or Prothrombin Time ≤ 1.5 times ULN
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN
  • Serum albumin ≥ 30 g/L
  • Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose and must be willing to use highly effective contraception during the trial and for 120 days after the last dose. Male subjects with partners of childbearing potential must be surgically sterilized or agree to use highly effective contraception during the trial and for 120 days after the last dose.

Who cannot join

  • Subjects with any of the following conditions are ineligible for inclusion in this study:
  • 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
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  • 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
  • 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.
  • Severe chronic or active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first study drug dose. Note: Antiviral therapy is permitted for patients with viral hepatitis.
  • Any condition requiring systemic treatment with corticosteroids (prednisone or equivalent >10 mg/day) or other immunosuppressive agents within ≤14 days prior to the first dose of study drug
  • Hypersensitivity to any component of tislelizumab, zanidatamab，capecitabine, S-1, oxaliplatin, or any component of the container
  • Any major surgery requiring general anesthesia within ≤28 days prior to the first dose of study drug
  • Bleeding, thrombotic disorders, or use of anticoagulants (e.g., warfarin) or similar agents requiring therapeutic INR monitoring within 6 months prior to the first dose of study drug
  • History of allogeneic stem cell transplantation or organ transplantation
  • Live vaccine administration within ≤28 days prior to the first study drug dose. Note: Seasonal influenza vaccines, broadly classified as inactivated vaccines, are permitted. Inactivated COVID-19 vaccines are permitted. mRNA COVID-19 vaccines are not permitted. Intranasal influenza vaccines are live vaccines and are not permitted.
  • Concurrent participation in another clinical study, unless it is an observational (non-interventional) study or the participant is in the follow-up period of an interventional study
  • Inability to swallow tablets or diseases significantly affecting gastrointestinal function
  • Pregnant or lactating women
  • Other conditions deemed ineligible by the investigator.
  • Locally Advanced Rectal Cancer Cohort:
  • Previous treatment for rectal cancer, or clinical or imaging evidence of existing or potential distant metastasis
  • Clinical or imaging evidence of intestinal obstruction, gastrointestinal perforation with bleeding, prior abdominal abscess, or recent (within 3 months) occurrence of gastrointestinal perforation, abdominal abscess, or intestinal obstruction; or investigator assessment indicating high risk of perforation or bleeding
  • Assessed by the investigator as initially unresectable or unable to tolerate surgery
  • Patient assessed by the investigator as having factors rendering them unsuitable for radiotherapy
  • The patient has ≥2 concurrent colorectal cancer lesions
  • Patient has contraindications for MRI examination
  • Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort:
  • Previous treatment for gastric/gastroesophageal junction cancer, or clinical/imaging evidence of existing or potential distant metastasis
  • Clinical or imaging evidence of intestinal obstruction, gastrointestinal perforation, or bleeding; prior abdominal abscess; or recent (within 3 months) gastrointestinal perforation, abdominal abscess, or intestinal obstruction; or investigator assessment indicating high risk of perforation or bleeding
  • Initial inoperability as assessed by the investigator, or inability of the patient to tolerate surgery
  • Advanced colorectal cancer cohort:
  • Patients with any prior histopathological or hematological ctDNA testing demonstrating mismatch repair gene deficiency (dMMR) or microsatellite instability (MSI-H)
  • Presence of active leptomeningeal disease or uncontrolled brain metastases. Patients with previously treated brain metastases may be eligible if imaging shows stability, confirmed by repeat imaging demonstrating no progression for at least 4 weeks (Note: repeat imaging must occur during the study screening period).

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Zhenyu Lin, Ph.D. contact

027-85871982

whxhlzy@hust.edu.cn

Tao Zhang, Ph.D. contact

taozhangxh@hust.edu.cn

About this study

Official title: A Prospective, Multi-cohort Clinical Study to Explore the Preliminary Efficacy and Safety of Zanidatamab in Combination With Tislelizumab for HER2-Positive GI Tumors: the UNION-HER2-BASKET Study

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.

Read the detailed description

This study is a prospective, multi-cohort clinical trial designed to explore the preliminary efficacy and safety of zanidatamab combined with tislelizumab and chemoradiotherapy in patients with HER2-positive locally advanced or metastatic gastrointestinal tumors. The study comprises three cohorts: ①Locally Advanced Rectal Cancer Cohort: Evaluate the preliminary efficacy of zanidatamab combined with tislelizumab and chemoradiotherapy for neoadjuvant and organ-preserving therapy in patients with HER2-positive locally advanced rectal cancer, as measured by investigator-assessed complete response rate (CR rate).②Locally Advanced Gastric/Gastroesophageal Junction Cancer Cohort:Evaluate the preliminary efficacy of zanidatamab combined with tislelizumab and chemotherapy for neoadjuvant treatment in patients with HER2-positive locally advanced gastric/gastroesophageal junction cancer based on investigator-assessed pathological complete response rate (pCR rate).③Advanced-line colorectal cancer cohort: Evaluate the preliminary efficacy of zanidatamab combined with tislelizumab in patients with HER2-positive advanced-line colorectal cancer based on investigator-assessed progression-free survival (PFS).

Being tested
short-course radiotherapy, Zanidatamab, Tisleizumab(BGB-A317), Capecitabine, Oxaliplatin
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • short-course radiotherapyRadiation

    25Gy, 5Gy×5

  • ZanidatamabDrug

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

  • Tisleizumab(BGB-A317)Drug

    200 mg，IV，D1，Q3W

  • CapecitabineDrug

    1000mg/m2/time，BID，PO，D1-14, Q3W

  • OxaliplatinDrug

    130 mg/m2/次，IV，D1, Q3W

  • TME surgeryProcedure or surgery

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

  • S-1Drug

    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）

  • D2Procedure or surgery

    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.

Study groups in NCT07243938
Study groupRoleWhat they receive
Locally Advanced Rectal Cancer CohortExperimentalAll 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.
Receives: Radiation: short-course radiotherapy; Drug: Zanidatamab; Drug: Tisleizumab(BGB-A317); Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery
Locally Advanced Gastric/Gastroesophageal Junction Cancer CohortExperimentalSubjects 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.
Receives: Drug: Zanidatamab; Drug: Tisleizumab(BGB-A317); Drug: Oxaliplatin; Drug: S-1; Procedure: D2
Advanced colorectal cancer cohortExperimentalSubjects 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.
Receives: Drug: Zanidatamab

What is being measured

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

  1. 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.

    Measured: 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).

  2. Pathological Complete Response Rate (pCR Rate)

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

    Measured: Within 15 weeks

  3. 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

    Measured: Within 2 years

Secondary outcomes (2)

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

    Adverse events and surgical safety

    Measured: an expected average of 2 years

  2. 3-year disease-Free Survival

    The time from the first day of disease free (operation date) to local or distant recurrence, or the death event caused by any reason, whichever occurs first time.

    Measured: an expected average of 3 years

Timeline

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

  1. First posted24 Nov 2025
  2. Study start15 Jan 2026 (estimated)
  3. Primary completion30 Jul 2028 (estimated)
  4. Study completion1 Jun 2031 (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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07243938
Sponsor's protocol ID
UNION-HER2-BASKET
Status last verified
Nov 2025
First submitted
14 Nov 2025
Last updated
24 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing short-course radiotherapy, Zanidatamab and Tisleizumab(BGB-A317) in people with Locally Advanced Rectal Cancer (LARC) and Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma, run by Tao Zhang.

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 33 inclusion and 41 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 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

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 Zhenyu Lin, Ph.D. (027-85871982, whxhlzy@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response Rate (CR Rate) (time frame: 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).). The study lists 3 primary outcomes in all. 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 NCT07243938.

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 24 Nov 2025.

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