tarlatamab — Drug Monograph

Tarlatamab (Imdelltra) — DLL3 Bispecific for ES-SCLC

Tarlatamab (Imdelltra) is a DLL3-directed bispecific T-cell engager (BiTE) for relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC). It binds DLL3 (Delta-like ligand 3), which is overexpressed on ~85% of SCLC tumors but absent on normal adult tissues, and CD3 on T cells, redirecting cytotoxic T cells to kill DLL3-expressing cancer cells. Because T-cell activation can trigger cytokine release syndrome (CRS) and ICANS, tarlatamab uses an intravenous step-up schedule with mandatory facility monitoring. This monograph covers tarlatamab indications in ES-SCLC, DLL3 surface expression and the BiTE mechanism, step-up dosing, hospitalization/observation guidelines, and CRS/ICANS mitigation.

Indications (FDA / NCCN)

• Relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC) after platinum-based chemotherapy (DeLLphi-301)
• FDA accelerated approval (May 2024)
• DLL3-directed BiTE — off-the-shelf, no lymphodepletion required

Dosing

• IV step-up: 1 mg (C1D1) → 10 mg (C1D8) → 10 mg every 2 weeks (C2D1 onward)
• Each dose given over 1 hour
• Premedicate with dexamethasone 8 mg IV + antipyretic/antihistamine before C1D1 and C1D8
• Give 1 L normal saline IV after the two step-up doses

Monitoring

• Continuous facility monitoring 22–24 h after C1D1 and C1D8; within 1 h of care for 48 h
• CRS (fever, hypotension, hypoxia) for ≥48 h after each step-up dose
• ICANS / neurologic toxicity; do not dose outpatient until step-up complete
• Tapered post-infusion monitoring for later cycles if no prior Grade ≥2 CRS/ICANS

Brand names: Imdelltra

Drug class: Other

Mechanism of Action

Bispecific T-cell engager (BiTE) that simultaneously binds DLL3 (Delta-like ligand 3) on tumor cells and CD3ε on T cells, redirecting cytotoxic T cells to kill DLL3-expressing cancer cells. DLL3 is overexpressed in ~85% of SCLC tumors and is absent on normal adult tissues, providing tumor selectivity.

FDA Indications

• Relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC) after platinum-based chemotherapy (FDA accelerated approval May 2024, based on DeLLphi-301: 40% ORR, median duration of response 9.9 months in the 10 mg cohort)

Common Side Effects

• CRS (51%)
• Fatigue
• Pyrexia
• Anemia
• Decreased appetite
• Constipation
• Nausea
• Peripheral neuropathy
• Arthralgia

Clinical Pearl

DLL3 is a Notch ligand that is highly expressed in SCLC and other high-grade neuroendocrine carcinomas but minimally expressed in normal adult tissues. The step-up dosing schedule (1 mg → 10 mg) was specifically designed to reduce the risk and severity of CRS. Unlike CAR-T cells, BiTEs do not require lymphodepletion and are "off-the-shelf" treatments.

Related Therapies & Mechanisms

• Lurbinectedin (Zepzelca) — Other · SCLC
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other
• Asparaginase (L-asparaginase, E. coli) (Elspar) — Other