TELISOTUZUMAB VEDOTIN-TLLV INJ,LYPHL

Clinical Criteria Summary

Previously treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
High c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining]
Currently approved under accelerated approval

1.9 mg/kg intravenously every 2 weeks
Continue until disease progression or unacceptable toxicity
Available as 20 mg or 100 mg telisotuzumab vedotin as lyophilized powder in a single-dose vial

Monitor for vision changes, dry eye, and other ocular symptoms; hold or consider discontinuation according to severity
Ensure adequate venous access or administer via central line to reduce discomfort associated with infusion
Assess ECOG performance status (0-1) and prior systemic therapy lines (1-2 lines, including 1 line of cytotoxic chemotherapy)

No boxed warnings or contraindications listed
Embryo-fetal toxicity: Can cause fetal harm in a pregnant woman; advise effective contraception
Peripheral neuropathy: Occurred in 51% of patients (11% grade 3); led to discontinuation in 13%
ILD/pneumonitis: Occurred in 10% of patients (3% grade 3, 0.6% grade 4); led to discontinuation in 7%
Infusion-related reactions: Occurred in 3% of patients (1.2% grade 3, 0.6% grade 4); led to discontinuation in 0.6%

Pre-medications recommended for patients who experience an infusion-related reaction (administered 30-60 minutes prior to subsequent infusions): Diphenhydramine 25-50mg PO/IV, Famotidine 20mg PO/IV, Acetaminophen 650-1,000mg PO/IV, Methylprednisolone 125mg IV (or equivalents)
Adverse events occurring in ≥20% of patients: decreased albumin, increased glucose, peripheral neuropathy, decreased calcium, increased ALT, decreased lymphocytes, increased GGT, decreased hemoglobin, increased AST, decreased phosphorous/sodium, increased alkaline phosphatase, fatigue, peripheral edema, decreased appetite
Fatal events (5%): ILD/pneumonitis, pneumonia, sudden death, noninfectious endocarditis, myocardial infarction

Radiation therapy to the lungs within 6 months
History of interstitial lung disease (ILD) or pneumonitis requiring steroids, or prior ILD or pneumonitis within 3 months
Unresolved grade ≥2 adverse events
Major surgery within 3 weeks

c-Met protein expression is not currently routinely evaluated in VHA
Risk vs. benefit analysis should be considered due to notable incidence of fatal adverse events and pending phase III data (TeliMET NSCLC-01)
Currently not listed in VA Oncology Clinical Pathways; c-Met overexpression not mentioned in pathways

Absolute neutrophil count (ANC) <1,000/mm3 (unless Duffy null phenotype), platelets <100,000/mm3
CrCl <30 mL/minute
Moderate or severe hepatic impairment: total bilirubin >1.5 times ULN and any AST or with liver metastases: total bilirubin >1.5 times ULN, or AST or ALT >5 times ULN
Symptomatic or unstable brain metastases
History of interstitial lung disease (ILD) or pneumonitis requiring steroids, or prior ILD or pneumonitis within 3 months
Evidence of pulmonary fibrosis
Grade ≥2 or history of Grade ≥3 peripheral neuropathy
Known pregnancy
Lactating

Locally-advanced or metastatic non-squamous EGFR-wildtype non-small cell lung cancer (NSCLC)
High c-Met protein overexpression (≥50% of tumor cells with strong 3+ staining)
Progression on prior systemic cytotoxic chemotherapy and immunotherapy

For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 2 months after stopping treatment for women and 4 months after for men.