Advanced Biliary Tract CancerPhase 2NCT07723534
Zolbetuximab With mFOLFOX6 or CAPOX in Claudin 18.2 Overexpressed Advanced or Metastatic Biliary Tract Cancers
A Phase 2 study testing Zolbetuximab, mFOLFOX6 and CAPOX in people with Advanced Biliary Tract Cancer and Metastatic Biliary Tract Carcinoma, run by Midhun Malla at 1 site in United States.
Trial summary
Subjects will receive zolbetuximab with either CAPOX every 3 weeks or mFOLFOX6 every 2 weeks. The chemotherapy regimen chosen, mFOLFOX6 or CAPOX is per the treating investigator discretion and subject preference. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Biliary Tract Cancer, Metastatic Biliary Tract Carcinoma
- What is being tested?
- Zolbetuximab, mFOLFOX6 and CAPOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Aug 2030
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years at the time of informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at the time of registration.
- Histological or cytological confirmation of biliary tract carcinoma per American Joint Committee on Cancer (AJCC) staging manual v8.
- Radiologically confirmed locally advanced/unresectable (per treating investigator) or metastatic disease.
- Evaluable disease per RECIST 1.1.
- Expression of Claudin 18.2 (CLDN18.2) in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemical testing (IHC) from a CLIA certified lab using the VENTANA CLDN18 (43-14A) antibody (Roche Diagnostics). NOTE: A paraffin block or at least 5 unstained glass "positively charged" slides with 4-microns formalin-fixed, paraffin-embedded tissue are required for testing. Tissue must be from diagnosis via standard biopsy or surgery. Specimens that are from fine-needle aspirate (FNA), cytology, or metastatic bone lesions do not qualify for CLDN18.2 staining. If archival tissue is not available and the subject is undergoing a standard of care biopsy, part of that tissue may be used for testing. If tissue for Claudin 18.2 testing is not available, the subject is not eligible for the trial.
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- Receipt of only one prior line of systemic therapy for advanced disease. NOTE: Patients who received a single dose of mFOLFOX6 or CAPOX chemotherapy prior to registration may still be eligible for the trial, provided the tissue for CLDN18.2 for testing was obtained prior to the cycle of chemotherapy.
- Prior cancer treatment must be completed at least 14 days prior to start of study treatment.
- Recovery from all adverse events of the prior systemic therapy (other than alopecia) to grade ≤ 1 or baseline. NOTE: Known peripheral sensory neuropathy ≤ Grade 1 is allowed if the absence of deep tendon reflexes is the sole neurological abnormality.
- Demonstrate adequate organ function at the time of screening as defined below.
- Hematological
- Platelets (Plt) ≥ 100,000 /mm3
- Absolute Neutrophil Count (ANC) ≥ 1500 K/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Renal
- Calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula will be used to calculate creatinine clearance)
- Hepatic
- Total bilirubin ≤ 2 g/dl
- Aspartate aminotransferase (AST) ≤ 2.5 × ULN without liver metastases and ≤ 5x ULN if liver metastases are present
- Alanine aminotransferase (ALT) ≤ 2.5 × ULN without liver metastases and ≤ 5x ULN if liver metastases are present
- Coagulation
- International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN except for subjects receiving anticoagulation therapy.
- Other
- Albumin ≥ 2.5 g/dL
Who cannot join
- Receipt of 5-fluorouracil or capecitabine in the adjuvant setting within 6 months prior to registration or patients who progressed on FOLFOX or CAPOX regimens in the past.
- Previous treatment with Claudin 18.2 directed treatment.
- Active infection requiring systemic therapy. NOTE: Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
- Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the subject is being treated on study.
- Active central nervous system (CNS) metastases. NOTE: A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to registration, have been off corticosteroids (≤ 10 mg/day oral prednisone or equivalent) for ≥ 2 weeks, and are asymptomatic.
- Known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment or other monoclonal antibody.
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- Known dihydropyrimidine dehydrogenase (DPD) deficiency. NOTE: Screening for DPD deficiency may be conducted per local requirements but is not required.
- Treatment with any investigational drug within 7 days prior to registration.
- Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen.
- Subject has significant cardiovascular disease, including any of the following:
- Congestive heart failure (defined as New York Heart Association [NYHA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to registration
- History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)
- History or family history of congenital long QT syndrome
- Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 28 days prior to registration are eligible.)
- Major surgical procedure ≤ 28 days prior to registration.
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimen.
- Known psychiatric illness or social situations such as incarceration that would preclude study compliance, per investigator judgment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35233
About this study
Official title: A Single Arm Phase II Trial of Zolbetuximab in Combination With mFOLFOX6 or CAPOX Chemotherapy in Claudin 18.2 Overexpressed Advanced or Metastatic Biliary Tract Cancers
Subjects will receive zolbetuximab with either CAPOX every 3 weeks or mFOLFOX6 every 2 weeks. The chemotherapy regimen chosen, mFOLFOX6 or CAPOX is per the treating investigator discretion and subject preference.
Study treatment will continue for a maximum of 2 years, or until disease progression per RECIST 1.1, intolerable side effects, or investigator/subject preference. Disease evaluation will occur every 8 to 9 weeks.
- Being tested
- Zolbetuximab, mFOLFOX6, CAPOX
- Keywords
- Overexpressed Claudin 18.2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZolbetuximabDrug
Zolbetuximab (800 mg/m^2) will be administered with CAPOX or mFOLFOX6 for Cycle 1. When administered with CAPOX, for every subsequent cycle Zolbetuximab (600 mg/m^2) will be administered. When administered with mFOLFOX6, for every subsequent cycle Zolbetuximab (400 mg/m^2).
mFOLFOX6Drug
Oxaliplatin (85 mg/m^2), Leucovorin (400 mg/m^2), and 5-FU (5-fluorouracil) continuous infusion (2400 mg/m^2) will be administered every 2 weeks.
CAPOXDrug
Oxaliplatin (130 mg/m^2) and Capecitabine (750-800 mg/m^2) will be administered every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Zolbetuximab and CAPOX or mFOLFOX6 | Experimental | Subjects will receive zolbetuximab with CAPOX every 3 weeks or with mFOLFOX6 every 2 weeks. Receives: Drug: Zolbetuximab; Drug: mFOLFOX6; Drug: CAPOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) rate
PFS will be defined as the percentage of evaluable patients alive and progression-free (radiologically per RECIST 1.1 or clinically per treating investigator discretion) at 6 months from date of registration.
Measured: 6 months
Secondary outcomes (5)
Median Progression Free Survival (PFS)
Median PFS is defined as time from registration to date of radiological (per RECIST 1.1) or clinical (per treating investigator discretion) progression or death from any cause, whichever comes first.
Measured: 24 months
Overall Survival (OS)
- OS will be defined as time from registration to either date of death due to any cause or last follow-up date.
Measured: 24 months
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects, in the evaluable population, who achieve a complete or partial response (CR or PR), per RECIST v 1.1.
Measured: 24 months
Disease Control Rate (DCR)
DCR is defined as the proportion of subjects, in the evaluable population, who achieve a complete or partial response (CR or PR), or stable disease (SD) per RECIST v1.1.
Measured: 24 months
Adverse Events
Adverse events and reportable serious events are defined by the study protocol per NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2026
- Study startNov 2026 (estimated)
- Primary completionFeb 2029 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Biliary Tract CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Model description
- Subjects will receive zolbetuximab with either CAPOX every 3 weeks or mFOLFOX6 every 2 weeks. The chemotherapy regimen chosen, mFOLFOX6 or CAPOX is per the treating investigator discretion and subject preference.
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Midhun Malla
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alabama at Birmingham, Astellas Pharma Inc, University of Michigan
- Responsible party
- Sponsor-investigator, Midhun Malla, Hoosier Cancer Research Network
- Investigators
- Midhun Malla, MD, MS, Principal investigator, University of Alabama at BirminghamVaibhav Sahai, MBBS, MS, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07723534
- Sponsor's protocol ID
- HCRN-GI24-690
- Status last verified
- Oct 2026
- First submitted
- 20 Jul 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Phase II Trial of Zolbetuximab in Combination With mFOLFOX6 or CAPOX Chemotherapy in Claudin 18.2 Overexpressed Advanced or Metastatic Biliary Tract Cancers
- ClinicalTrials.gov ID
- NCT07723534
- Acronym / sponsor ID
- HCRN-GI24-690
- Keywords
- Overexpressed Claudin 18.2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Midhun MallaUniversity, hospital or other
- Collaborators
- University of Alabama at Birmingham, Astellas Pharma Inc, University of Michigan
- Study start
- Nov 2026 (estimated)
- Primary completion
- Feb 2029 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 23 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subjects will receive zolbetuximab with either CAPOX every 3 weeks or mFOLFOX6 every 2 weeks. The chemotherapy regimen chosen, mFOLFOX6 or CAPOX is per the treating investigator discretion and subject preference.
Study treatment will continue for a maximum of 2 years, or until disease progression per RECIST 1.1, intolerable side effects, or investigator/subject preference. Disease evaluation will occur every 8 to 9 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Subjects will receive zolbetuximab with either CAPOX every 3 weeks or mFOLFOX6 every 2 weeks. The chemotherapy regimen chosen, mFOLFOX6 or CAPOX is per the treating investigator discretion and subject preference.
| Arm | Type | Receives |
|---|---|---|
| Zolbetuximab and CAPOX or mFOLFOX6 | Experimental | Drug: Zolbetuximab, Drug: mFOLFOX6, Drug: CAPOXSubjects will receive zolbetuximab with CAPOX every 3 weeks or with mFOLFOX6 every 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Age ≥ 18 years at the time of informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at the time of registration.
- Histological or cytological confirmation of biliary tract carcinoma per American Joint Committee on Cancer (AJCC) staging manual v8.
- Radiologically confirmed locally advanced/unresectable (per treating investigator) or metastatic disease.
- Evaluable disease per RECIST 1.1.
Key exclusion criteria (17 listed)
- Receipt of 5-fluorouracil or capecitabine in the adjuvant setting within 6 months prior to registration or patients who progressed on FOLFOX or CAPOX regimens in the past.
- Previous treatment with Claudin 18.2 directed treatment.
- Active infection requiring systemic therapy. NOTE: Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
- Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the subject is being treated on study.
- Active central nervous system (CNS) metastases. NOTE: A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to registration, have been off corticosteroids (≤ 10 mg/day oral prednisone or equivalent) for ≥ 2 weeks, and are asymptomatic.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZolbetuximabZolbetuximab (800 mg/m^2) will be administered with CAPOX or mFOLFOX6 for Cycle 1. When administered with CAPOX, for every subsequent cycle Zolbetuximab (600 mg/m^2) will be administered. When administered with mFOLFOX6, for every subsequent cycle Zolbetuximab (400 mg/m^2). | Drug | Zolbetuximab and CAPOX or mFOLFOX6 |
| mFOLFOX6Oxaliplatin (85 mg/m^2), Leucovorin (400 mg/m^2), and 5-FU (5-fluorouracil) continuous infusion (2400 mg/m^2) will be administered every 2 weeks. | Drug | Zolbetuximab and CAPOX or mFOLFOX6 |
| CAPOXOxaliplatin (130 mg/m^2) and Capecitabine (750-800 mg/m^2) will be administered every 3 weeks. | Drug | Zolbetuximab and CAPOX or mFOLFOX6 |
Primary outcome
Progression free survival (PFS) rate
Time frame: 6 months
PFS will be defined as the percentage of evaluable patients alive and progression-free (radiologically per RECIST 1.1 or clinically per treating investigator discretion) at 6 months from date of registration.
5 secondary outcomes
Median Progression Free Survival (PFS)
Time frame: 24 months
Overall Survival (OS)
Time frame: 24 months
Objective Response Rate (ORR)
Time frame: 24 months
Disease Control Rate (DCR)
Time frame: 24 months
Adverse Events
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Midhun Malla, MD, MS principal investigator
University of Alabama at Birmingham
Vaibhav Sahai, MBBS, MS principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zolbetuximab, mFOLFOX6 and CAPOX in people with Advanced Biliary Tract Cancer and Metastatic Biliary Tract Carcinoma, run by Midhun Malla at 1 site in United States.
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 24 inclusion and 17 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 2 Nov 2026. 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 United States. 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 Midhun Malla, MD, MS (205-996-9740, midhunmalla@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Nov 2026.