ZOLBETUXIMAB-CLZB INJ,LYPHL
Clinical Criteria Summary
Document 729
Exclusion Criteria
- PD-L1 by Combined Positive Score (CPS) > 5 (unless patient is not a candidate for an immune checkpoint inhibitor)
- Prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies
- Absolute Neutrophil Count < 1500/mm3
- Platelets < 100,000/mm3
- Total bilirubin > 1.5x Upper Limit of Normal (or > 3x Upper Limit of Normal with liver metastases)
- Estimated Creatinine Clearance < 30ml/min
- Lactation
Inclusion Criteria
- Locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma
- HER2-negative tumor
- CLDN18.2 positive tumor (≥75% of tumor cells showing moderate-to-strong staining)
- Treatment plan includes zolbetuximab with a fluoropyrimidine- and platinum-based regimen (i.e. mFOLFOX6 or CAPOX) as first-line therapy
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (if applicable)
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment; treatment should be given if the benefit outweighs the potential risk
- For females who are lactating: breastfeeding/providing breastmilk to an infant is not recommended during therapy and for 8 months after stopping treatment.
Document 730
Indication & Patient Selection
- First-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) negative gastric or gastroesophageal junction adenocarcinoma
- Tumors must be CLDN18.2 positive, as determined by an FDA-approved test
- Administered in combination with fluoropyrimidine and platinum-containing chemotherapy (mFOLFOX6 or CAPOX)
Dosing & Administration
- Initial dose: 800 mg/m2 IV
- Subsequent doses: 600 mg/m2 IV every 3 weeks or 400 mg/m2 IV every 2 weeks
- Continue therapy until disease progression or unacceptable toxicity
- Supplied as 100 mg lyophilized powder in a single-dose vial
Monitoring & Safety Management
- Monitor patients during the infusion and for 2 hours afterwards (or longer as needed) for hypersensitivity and infusion-related reactions
- Pretreat patients with antiemetics prior to each infusion due to the highly emetogenic chemotherapy regimen
- Manage nausea and vomiting with antiemetics, fluid replacement, infusion interruptions, and infusion rate adjustments
Clinical Pathway & Guideline Recommendations
- NCCN Guidelines: Listed as a preferred first-line category 1 regimen for HER2-negative, CLDN18.2 positive locally advanced, unresectable, or metastatic gastric or GEJ cancer in combination with chemotherapy
- VA Oncology Clinical Pathway (Esophageal Cancer V1.2025): Recommended first-line for stage IVB adenocarcinoma (HER2 negative, MSS) in patients who are candidates for cytotoxic chemotherapy, test positive for CLDN18.2, and are not candidates for immunotherapy or have PD-L1 CPS <5%