What are the guidelines for using Tarlatamab (therapeutic antibody) in treatment?

Tarlatamab Guidelines for Treatment of Small Cell Lung Cancer

Tarlatamab is recommended as a preferred single-agent therapy for patients with relapsed small cell lung cancer (SCLC) who have received at least two prior lines of therapy, with a recommended dose of 10 mg intravenously every 2 weeks. 1

Indications and Patient Selection

Tarlatamab is FDA-approved for patients with relapsed SCLC who have received at least two prior lines of therapy. It is a bispecific T-cell engager that targets delta-like ligand 3 (DLL3) on cancer cells and CD3 on T cells, allowing the immune system to attack the cancer.

• Patient eligibility criteria:
  • Relapsed SCLC after ≥2 prior lines of therapy
  • Both platinum-sensitive and platinum-resistant disease (response rates of 31% and 52%, respectively) 1
  • Can be considered for patients with untreated brain metastases (based on emerging evidence) 2

Dosing and Administration Protocol

The recommended tarlatamab regimen follows a step-up dosing approach:

1. Initial 1 mg dose intravenously on day 1 of cycle 1
2. 10 mg dose on days 8 and 15 of cycle 1
3. 10 mg every 2 weeks thereafter until disease progression or unacceptable toxicity 1

Important: Inpatient monitoring is recommended for 24 hours after the first two doses of cycle 1 (days 1 and 8) due to risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). 1

Efficacy Data

In the phase 2 DeLLphi-301 trial:

• Overall response rate: 40% at 10 mg dose 1, 3
• Median duration of response: 9.7 months 1
• Median progression-free survival: 4.9 months 1, 3
• 9-month overall survival rate: 68% 1, 3
• Responses were durable with 59% of responders maintaining response for ≥6 months 3

Adverse Events Management

1. Cytokine Release Syndrome (CRS)

• Incidence: 51% of patients (30% grade 1,20% grade 2,1% grade 3) 1
• Timing: Median onset 13 hours after infusion, median duration 4 days 1
• Symptoms: Fever (97%), hypotension (20%), hypoxia (17%) 1
• Management:
  • Antipyretics (acetaminophen)
  • IV hydration
  • Glucocorticoids for more severe cases 4
  • Nearly all CRS events occurred during the first cycle 1

2. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

• Incidence: 8% of patients, all grade 1 or 2 1
• Timing: Median onset 5 days, mostly during cycle 1 1
• Management:
  • Close monitoring for neurological symptoms
  • Supportive care
  • Glucocorticoids for more severe cases

3. Other Common Adverse Events

• Decreased appetite (36%)
• Pyrexia (38%)
• Dysgeusia (32%)
• Anemia (30%)
• Neutropenia (16%) 4

Monitoring Recommendations

1. Pre-treatment evaluation:

   • Complete blood count
   • Comprehensive metabolic panel
   • Assessment for active infections

2. During treatment:

   • Inpatient monitoring for 24 hours after first two doses (days 1 and 8 of cycle 1)
   • Regular monitoring of complete blood counts
   • Assessment for signs/symptoms of CRS and ICANS
   • Evaluation of treatment response every 6-8 weeks

3. Patient education:

   • Report fever immediately
   • Report any neurological symptoms (confusion, difficulty speaking, seizures)
   • Report signs of infection

Comparative Efficacy

Tarlatamab joins topotecan and lurbinectedin as FDA-approved agents for relapsed SCLC. Cross-trial comparisons suggest that tarlatamab has a longer duration of response (>9 months) compared to other agents, though no direct head-to-head comparisons exist yet. 1

The DeLLphi-304 trial comparing tarlatamab with standard chemotherapy in relapsed SCLC is ongoing to address the question of comparative efficacy. 1

Special Populations

• Brain metastases: Emerging evidence suggests tarlatamab may be effective for patients with untreated brain metastases from SCLC, with 90% of patients showing clinical response or stability in a small case series. 2

• Quality of life impact: Patient-reported outcomes from the DeLLphi-301 trial showed stabilization or improvement in quality of life measures, including reduced symptom burden for dyspnea and stabilization for chest pain and cough. 5

Common Pitfalls and Caveats

1. CRS management: Failure to monitor for CRS during the first cycle, particularly after the first two doses, can lead to severe complications. Ensure proper monitoring and have management protocols in place.

2. Dosing schedule: The step-up dosing approach (1 mg → 10 mg) is critical to reduce the risk of severe CRS. Do not start with the full 10 mg dose.

3. Treatment discontinuation: Only 3% of patients discontinued tarlatamab due to treatment-related adverse events, suggesting most side effects can be managed with appropriate supportive care. 3

4. Patient selection: While tarlatamab shows promising efficacy, it should be reserved for patients who have received at least two prior lines of therapy, per FDA approval and clinical evidence.