TARLATAMAB-DLLE INJ,LYPHL

Clinical Criteria Summary

Extensive-stage small cell lung cancer (ES-SCLC) in adult patients with disease progression on or after platinum-based chemotherapy (granted accelerated approval).

Adults with histologically or cytologically confirmed SCLC.
Recurrent or relapsed disease following at least one platinum-based treatment and at least one other line of therapy.
Good performance status (ECOG PS 0-1).
Symptomatic brain metastases are an exclusion criterion; asymptomatic brain metastases are acceptable.

Administered intravenously over one hour at a constant flow rate using an infusion pump.
Cycle 1 step-up dosing: Day 1 (1 mg), Day 8 (10 mg), Day 15 (10 mg). Cycles 2 and onward: Day 1 and Day 15 (10 mg each). Each cycle is 28 days.
Only qualified healthcare professionals with appropriate medical support capable of managing severe reactions (CRS, ICANS) should administer the drug.
Patients must be well hydrated prior to administration.

Cycle 1: Dexamethasone 8 mg IV (or equivalent) administered within one hour prior to tarlatamab on Days 1 and 8.
Cycle 1: Normal saline 1 liter IV over 4-5 hours administered immediately after completion of tarlatamab on Days 1, 8, and 15.

Monitor for 22 to 24 hours from the start of infusion on Cycle 1 Day 1.
Patients should remain within one hour of an appropriate healthcare setting accompanied by a caregiver for 48 hours following the first infusion.
Extended monitoring is required if Grade ≥2 cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or neurological toxicity occurs during prior treatments.
Monitor complete blood counts at baseline, prior to each dose, and as clinically indicated; withhold or permanently discontinue based on severity of cytopenias.
Monitor for infections at baseline, during treatment, and as clinically indicated; withhold or permanently discontinue based on severity.
Monitor liver enzymes and bilirubin at baseline, prior to each dose, and as clinically indicated; withhold or permanently discontinue based on severity of hepatotoxicity.
Monitor for hypersensitivity reactions during treatment; withhold or permanently discontinue based on severity.
Patients must avoid driving and operating heavy machinery until neurological symptoms resolve.

Pregnancy: Females of reproductive potential must undergo pregnancy testing prior to treatment initiation. Effective contraception is required during treatment and for two months after the last dose due to potential fetal harm.
Lactation: Breastfeeding is contraindicated during treatment and for two months after the last dose.
Pediatric use: Safety and efficacy have not been established.
Contraindications: None stated.

Recommended following failure of first-line chemotherapy and an initial subsequent line of therapy.
Per VA Clinical Pathways: Indicated for patients with good performance status (ECOG PS 0-1) who have failed retreatment with a platinum-based doublet (if chemo-sensitive) and lurbinectedin.
Per NCCN guidelines: Not a preferred agent in chemo-sensitive disease; listed as another recommended regimen after re-treatment with a first-line platinum-based doublet. In chemo-resistant disease, listed as a preferred regimen alongside lurbinectedin and topoisomerase inhibitors.
Initial treatment with lurbinectedin or topotecan is reasonable before administering tarlatamab due to cost and safety profile considerations.

Facility is not equipped to monitor and manage Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), if necessary
Patient is unable to be monitored during and for 22-24 hours after step-up doses on Cycle 1 Day 1 and Day 8 at an appropriate healthcare setting
Patient is unable to stay within 1 hour of an appropriate healthcare facility for 48 hours after Cycle 1 Day 1 and Day 8 infusions
Untreated or symptomatic brain metastases and leptomeningeal disease
Prior recurrent grade 2 or higher pneumonitis or severe immunotherapy-related adverse events leading to discontinuation
Evidence of interstitial lung disease or active, non-infectious pneumonitis
Pregnancy
Lactation

Extensive stage small cell lung cancer with disease progression after first-line platinum-based chemotherapy
Care is provided by a VA/VA Community Care oncology or hematology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Goals of care and role of Palliative Care consult have been discussed and documented

For patients who can become pregnant and patients with partners who can become pregnancy: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment
For patients with treated brain metastases: definitive therapy must have been completed at least 2 weeks prior to treatment with no evidence of radiographic central nervous system progression afterwards