Zolbetuximab With mFOLFOX6 or CAPOX in Claudin 18.2 Overexpressed Advanced or Metastatic Biliary Tract Cancers

NCT07723534 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-GI24-690
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Biliary Tract Carcinoma; Advanced Biliary Tract Cancer

Keywords

Overexpressed Claudin 18.2

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (5)

• Median Progression Free Survival (PFS)

  24 months

• Overall Survival (OS)

  24 months

• Objective Response Rate (ORR)

  24 months

• Disease Control Rate (DCR)

  24 months

• Adverse Events

  24 months

Study Arms (1)

Zolbetuximab and CAPOX or mFOLFOX6

EXPERIMENTAL

Subjects will receive zolbetuximab with CAPOX every 3 weeks or with mFOLFOX6 every 2 weeks.

Drug: Zolbetuximab; Drug: mFOLFOX6; Drug: CAPOX

Interventions

Zolbetuximab DRUG

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).

Zolbetuximab and CAPOX or mFOLFOX6

mFOLFOX6 DRUG

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.

Zolbetuximab and CAPOX or mFOLFOX6

CAPOX DRUG

Oxaliplatin (130 mg/m\^2) and Capecitabine (750-800 mg/m\^2) will be administered every 3 weeks.

Zolbetuximab and CAPOX or mFOLFOX6

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Midhun Malla: lead
• University of Alabama at Birmingham: collaborator
• Astellas Pharma Inc: collaborator
• University of Michigan: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Interventions

zolbetuximab

Study Officials

• Midhun Malla, MD, MS

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Vaibhav Sahai, MBBS, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Midhun Malla, MD, MS

CONTACT

205-996-9740; midhunmalla@uabmc.edu

Amber Ryba

CONTACT

317-634-5842; aryba@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: 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 Record Dates

• First Submitted: July 20, 2026
• First Posted: July 23, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: July 24, 2026

Record last verified: 2026-07

Locations

US (1)