What are the guidelines for the use of tarlatamab?

Tarlatamab Use in Small Cell Lung Cancer

Tarlatamab is a preferred single-agent therapy for patients with relapsed small cell lung cancer (SCLC) after platinum-based chemotherapy, administered as 1 mg IV on day 1 of cycle 1, followed by 10 mg IV on days 8 and 15 of cycle 1, then 10 mg IV every 2 weeks thereafter until disease progression or unacceptable toxicity. 1

Indications and Patient Selection

For relapsed SCLC with chemotherapy-free interval <90 days:

• Tarlatamab is a preferred single-agent option alongside topotecan and lurbinectedin 1
• Single-agent therapy is preferred over multiagent regimens due to better risk-benefit balance 1

For relapsed SCLC with chemotherapy-free interval ≥90 days:

• Either rechallenge with platinum-based regimen OR single-agent therapy (tarlatamab, topotecan, or lurbinectedin) may be offered 1

Eligible patient characteristics from pivotal trial:

• Disease progression after ≥2 prior systemic regimens (one must be platinum-based) 1
• ECOG performance status 0-1 1
• Asymptomatic, previously treated, stable brain metastases are acceptable 1
• 73% of trial patients had prior immunotherapy 1

Exclusion criteria:

• Interstitial lung disease 1
• Active pneumonitis 1
• History of severe infusion reactions 1
• Grade ≥2 pneumonitis from prior immunotherapy 1

Dosing Regimen

Step-up dosing schedule (FDA-approved):

• Cycle 1, Day 1: 1 mg IV 1
• Cycle 1, Day 8: 10 mg IV 1
• Cycle 1, Day 15: 10 mg IV 1
• Subsequent cycles: 10 mg IV every 2 weeks until disease progression or unacceptable toxicity 1

Efficacy Outcomes

Response rates at 10 mg dose:

• Overall response rate: 40% 1
• Median duration of response: 9.7 months (substantially longer than other agents) 1
• Response in platinum-sensitive disease: 31% 1
• Response in platinum-resistant disease: 52% 1

Survival outcomes:

• Median progression-free survival: 4.9 months 1
• 9-month progression-free survival rate: 28% 1
• 9-month overall survival rate: 68% 1

Adverse Event Management

Cytokine Release Syndrome (CRS)

Incidence and timing:

• Occurs in 51% of patients (30% grade 1,20% grade 2,1% grade 3) 1
• Median onset: 13 hours after infusion 1
• Median duration: 4 days 1
• Nearly all events occur during first cycle 1

Clinical presentation:

• Fever (97% of CRS cases) 1
• Hypotension (20% of CRS cases) 1
• Hypoxia (17% of CRS cases) 1

Management strategy:

• Mandatory 24-hour inpatient monitoring after first two doses (cycle 1, days 1 and 8) 1
• Supportive care with antipyretics (acetaminophen) 2
• Intravenous hydration 2
• Glucocorticoids as needed 2

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Incidence and characteristics:

• Occurs in 8% of patients 1
• All events were grade 1 or 2 in severity 1
• Median onset: 5 days after infusion 1
• Predominantly occurs during cycle 1 1
• Grade 3 or higher ICANS: 0% at 10 mg dose 1

Other Common Adverse Events

Hematologic toxicity:

• Neutropenia: 16% of patients 2
• Grade ≥3 treatment-related adverse events: 26% of patients 1

Non-hematologic toxicity:

• Pyrexia: 38% 2
• Decreased appetite: 36% 2
• Dysgeusia: 32% 2
• Anemia: 30% 2

Treatment discontinuation:

• Only 3% discontinued due to treatment-related adverse events 3
• No deaths due to treatment-related adverse events in maintenance setting 4

Clinical Context and Positioning

Comparative effectiveness:

• Cross-trial comparisons suggest tarlatamab and lurbinectedin are more effective than topotecan 1
• Tarlatamab's median duration of response (>9 months) is substantially longer than other available agents 1
• Direct head-to-head comparison data are not yet available 1

Important caveats:

• The DeLLphi-304 trial comparing tarlatamab with standard chemotherapy is ongoing to provide definitive comparative efficacy data 1
• Tarlatamab represents one of only three FDA-approved agents for relapsed SCLC (alongside topotecan and lurbinectedin) 1
• The unique immune-mediated toxicity profile requires specific monitoring protocols, particularly during cycle 1 1